Details of the Researcher

PHOTO

Ayuko Hoshino
Section
Graduate School of Life Sciences
Job title
Professor
Degree

  • PhD (University of Tokyo)

Research History 13

  • 2026/10 - Present
    Tohoku University　Graduate School of Life Sciences　Professor (Cross Appointment)

  • 2024/04 - Present
    InaRIS: Inamori Research Institute for Science Fellowship　InaRIS Fellow

  • 2023/03 - Present
    The University of Tokyo　Research Center for Advanced Science and Technology　Professor

  • 2019/03 - 2023/03
    Weill Cornell Medicine　Adjunct Assistant Professor

  • 2020/03 - 2023/02
    Tokyo Institute of Technology　School of Life Science and Technology

  • 2019/04 - 2021/03
    The University of Tokyo

  • 2018/10 - 2019/02
    Weill Cornell Medicine　Instructor

  • 2016/04 - 2018/10
    Weill Cornell Medicine　Instructor, Susan Komen Postdoctoral スカラー

  • 2015/04 - 2016/03
    Weill Cornell Medicine　Research Associate, Susan Komen Postdoctoral スカラー

  • 2013/04 - 2015/03
    Weill Cornell Medicine　Postdoctoral Associate, 日本学術振興会海外特別研究員（RRA）

  • 2011/04 - 2015/03
    Weill Cornell Medicine,　Postdoctoral Associate

  • 2010/09 - 2011/03
    Weill Cornell Medicine　Visiting graduate student

  • 2009/04 - 2011/03
    東京大学大学院 新領域創成科学研究科 先端生命科学専攻 博士課程（日本学術振興会）　日本学術振興会特別研究員（DC2）

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Education 2

  • ニューヨーク大学タンドン工科大学

    2018/09 - 2020/05

  • 東京大学大学院　新領域創成科学研究科　先端生命科学専攻

    2009/04 - 2011/03

Professional Memberships 4

  • 日本女性科学者の会

  • 日本癌学会

  • American Association for Cancer Research

  • 日本神経科学学会

Research Areas 1

  • Life sciences / Molecular biology /

Awards 15

  1. 2021年度東工大挑戦的研究賞・末松特別賞

    2021/07　東京工業大学

  2. The Tokyo Academy of Physics Award 8th

    2025/06　The Tokyo University of Science

  3. 公益財団法人アステラス病態代謝研究会 竹中奨励賞

    2023/11　公益財団法人アステラス病態代謝研究会

  4. 第6回日本医療研究開発大賞 AMED理事長賞

    2023/08　内閣官房 健康・医療戦略室

  5. Forbes JAPAN WOMEN AWARD 2022 チェンジメーカー賞

    2022/10　Forbes JAPAN

  6. 第6回バイオインダストリー奨励賞

    2022/10　一般財団法人バイオインダストリー協会

  7. Johnson & Johnson Innovation The NAM Healthy Longevity 2022 QuickFire Challenge Accelerator Award

    2022/09　Johnson & Johnson Innovation, The National Academy of Medicine

  8. 第27回日本女性科学者の会奨励賞

    2022/05　日本女性科学者の会

  9. 第18回（令和3年度）日本学術振興会賞

    2022/02　日本学術振興会

  10. 2021年度 竹田若手研究者賞

    2021/12　竹田理化工業株式会社・東京工業大学生命理工学院

  11. 2021年度大隅ライフサイエンス研究会奨励賞

    2021/11　大隅ライフサイエンス研究会

  12. 第11回（2021年）フロンティアサロン永瀬賞 最優秀賞

    2021/09　一般財団法人フロンティアサロン財団

  13. Healthy Longevity Global Competition : Announcement of 2021 Catalyst Award Winners

    2021/09　The U.S. National Academy of Medicine

  14. 令和3年度文部科学大臣表彰若手科学者賞

    2021/04　文部科学省

  15. The 2nd Shining Female Researcher Award (President’s Award, Japan Science and Technology Agency)

    2020/11　Japan Science and Technology Agency

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Papers 32

  1. Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis. International-journal Peer-reviewed

    Gonçalo Rodrigues, Ayuko Hoshino, Candia M Kenific, Irina R Matei, Loïc Steiner, Daniela Freitas, Han Sang Kim, Peter R Oxley, Ilana Scandariato, Irene Casanova-Salas, Jinxiang Dai, Chaitanya R Badwe, Brunilde Gril, Milica Tešić Mark, Brian D Dill, Henrik Molina, Haiying Zhang, Alberto Benito-Martin, Linda Bojmar, Yonathan Ararso, Katharine Offer, Quincey LaPlant, Weston Buehring, Huajuan Wang, Xinran Jiang, Tyler M Lu, Yuan Liu, Joshua K Sabari, Sandra J Shin, Navneet Narula, Paula S Ginter, Vinagolu K Rajasekhar, John H Healey, Etienne Meylan, Bruno Costa-Silva, Shizhen Emily Wang, Shahin Rafii, Nasser Khaled Altorki, Charles M Rudin, David R Jones, Patricia S Steeg, Héctor Peinado, Cyrus M Ghajar, Jacqueline Bromberg, Maria de Sousa, David Pisapia, David Lyden

    Nature cell biology　21　(11)　1403-1412　2019/11

    DOI： 10.1038/s41556-019-0404-4 　

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    The development of effective therapies against brain metastasis is currently hindered by limitations in our understanding of the molecular mechanisms driving it. Here we define the contributions of tumour-secreted exosomes to brain metastatic colonization and demonstrate that pre-conditioning the brain microenvironment with exosomes from brain metastatic cells enhances cancer cell outgrowth. Proteomic analysis identified cell migration-inducing and hyaluronan-binding protein (CEMIP) as elevated in exosomes from brain metastatic but not lung or bone metastatic cells. CEMIP depletion in tumour cells impaired brain metastasis, disrupting invasion and tumour cell association with the brain vasculature, phenotypes rescued by pre-conditioning the brain microenvironment with CEMIP+ exosomes. Moreover, uptake of CEMIP+ exosomes by brain endothelial and microglial cells induced endothelial cell branching and inflammation in the perivascular niche by upregulating the pro-inflammatory cytokines encoded by Ptgs2, Tnf and Ccl/Cxcl, known to promote brain vascular remodelling and metastasis. CEMIP was elevated in tumour tissues and exosomes from patients with brain metastasis and predicted brain metastasis progression and patient survival. Collectively, our findings suggest that targeting exosomal CEMIP could constitute a future avenue for the prevention and treatment of brain metastasis.

  2. Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. International-journal Peer-reviewed

    Haiying Zhang, Daniela Freitas, Han Sang Kim, Kristina Fabijanic, Zhong Li, Haiyan Chen, Milica Tesic Mark, Henrik Molina, Alberto Benito Martin, Linda Bojmar, Justin Fang, Sham Rampersaud, Ayuko Hoshino, Irina Matei, Candia M Kenific, Miho Nakajima, Anders Peter Mutvei, Pasquale Sansone, Weston Buehring, Huajuan Wang, Juan Pablo Jimenez, Leona Cohen-Gould, Navid Paknejad, Matthew Brendel, Katia Manova-Todorova, Ana Magalhães, José Alexandre Ferreira, Hugo Osório, André M Silva, Ashish Massey, Juan R Cubillos-Ruiz, Giuseppe Galletti, Paraskevi Giannakakou, Ana Maria Cuervo, John Blenis, Robert Schwartz, Mary Sue Brady, Héctor Peinado, Jacqueline Bromberg, Hiroshi Matsui, Celso A Reis, David Lyden

    Nature cell biology　20　(3)　332-343　2018/03

    DOI： 10.1038/s41556-018-0040-4 　

    ISSN： 1465-7392

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    The heterogeneity of exosomal populations has hindered our understanding of their biogenesis, molecular composition, biodistribution and functions. By employing asymmetric flow field-flow fractionation (AF4), we identified two exosome subpopulations (large exosome vesicles, Exo-L, 90-120 nm; small exosome vesicles, Exo-S, 60-80 nm) and discovered an abundant population of non-membranous nanoparticles termed 'exomeres' (~35 nm). Exomere proteomic profiling revealed an enrichment in metabolic enzymes and hypoxia, microtubule and coagulation proteins as well as specific pathways, such as glycolysis and mTOR signalling. Exo-S and Exo-L contained proteins involved in endosomal function and secretion pathways, and mitotic spindle and IL-2/STAT5 signalling pathways, respectively. Exo-S, Exo-L and exomeres each had unique N-glycosylation, protein, lipid, DNA and RNA profiles and biophysical properties. These three nanoparticle subsets demonstrated diverse organ biodistribution patterns, suggesting distinct biological functions. This study demonstrates that AF4 can serve as an improved analytical tool for isolating extracellular vesicles and addressing the complexities of heterogeneous nanoparticle subpopulations.

  3. Metastasis: Lymphatic detours for cancer. International-journal Peer-reviewed

    Ayuko Hoshino, David Lyden

    Nature　546　(7660)　609-610　2017/06/28

    DOI： 10.1038/546609a 　

    ISSN： 0028-0836

    eISSN： 1476-4687

  4. Pre-metastatic niches: organ-specific homes for metastases. International-journal Peer-reviewed

    Héctor Peinado, Haiying Zhang, Irina R Matei, Bruno Costa-Silva, Ayuko Hoshino, Goncalo Rodrigues, Bethan Psaila, Rosandra N Kaplan, Jacqueline F Bromberg, Yibin Kang, Mina J Bissell, Thomas R Cox, Amato J Giaccia, Janine T Erler, Sachie Hiratsuka, Cyrus M Ghajar, David Lyden

    Nature reviews. Cancer　17　(5)　302-317　2017/05

    DOI： 10.1038/nrc.2017.6 　

    ISSN： 1474-175X

    eISSN： 1474-1768

  5. Tumour exosome integrins determine organotropic metastasis. International-journal Peer-reviewed

    Ayuko Hoshino, Bruno Costa-Silva, Tang-Long Shen, Goncalo Rodrigues, Ayako Hashimoto, Milica Tesic Mark, Henrik Molina, Shinji Kohsaka, Angela Di Giannatale, Sophia Ceder, Swarnima Singh, Caitlin Williams, Nadine Soplop, Kunihiro Uryu, Lindsay Pharmer, Tari King, Linda Bojmar, Alexander E Davies, Yonathan Ararso, Tuo Zhang, Haiying Zhang, Jonathan Hernandez, Joshua M Weiss, Vanessa D Dumont-Cole, Kimberly Kramer, Leonard H Wexler, Aru Narendran, Gary K Schwartz, John H Healey, Per Sandstrom, Knut Jørgen Labori, Elin H Kure, Paul M Grandgenett, Michael A Hollingsworth, Maria de Sousa, Sukhwinder Kaur, Maneesh Jain, Kavita Mallya, Surinder K Batra, William R Jarnagin, Mary S Brady, Oystein Fodstad, Volkmar Muller, Klaus Pantel, Andy J Minn, Mina J Bissell, Benjamin A Garcia, Yibin Kang, Vinagolu K Rajasekhar, Cyrus M Ghajar, Irina Matei, Hector Peinado, Jacqueline Bromberg, David Lyden

    Nature　527　(7578)　329-35　2015/11/19

    DOI： 10.1038/nature15756 　

    ISSN： 0028-0836

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    Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

  6. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. International-journal Peer-reviewed

    Bruno Costa-Silva, Nicole M Aiello, Allyson J Ocean, Swarnima Singh, Haiying Zhang, Basant Kumar Thakur, Annette Becker, Ayuko Hoshino, Milica Tešić Mark, Henrik Molina, Jenny Xiang, Tuo Zhang, Till-Martin Theilen, Guillermo García-Santos, Caitlin Williams, Yonathan Ararso, Yujie Huang, Gonçalo Rodrigues, Tang-Long Shen, Knut Jørgen Labori, Inger Marie Bowitz Lothe, Elin H Kure, Jonathan Hernandez, Alexandre Doussot, Saya H Ebbesen, Paul M Grandgenett, Michael A Hollingsworth, Maneesh Jain, Kavita Mallya, Surinder K Batra, William R Jarnagin, Robert E Schwartz, Irina Matei, Héctor Peinado, Ben Z Stanger, Jacqueline Bromberg, David Lyden

    Nature cell biology　17　(6)　816-26　2015/06

    DOI： 10.1038/ncb3169 　

    ISSN： 1465-7392

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    Pancreatic ductal adenocarcinomas (PDACs) are highly metastatic with poor prognosis, mainly due to delayed detection. We hypothesized that intercellular communication is critical for metastatic progression. Here, we show that PDAC-derived exosomes induce liver pre-metastatic niche formation in naive mice and consequently increase liver metastatic burden. Uptake of PDAC-derived exosomes by Kupffer cells caused transforming growth factor β secretion and upregulation of fibronectin production by hepatic stellate cells. This fibrotic microenvironment enhanced recruitment of bone marrow-derived macrophages. We found that macrophage migration inhibitory factor (MIF) was highly expressed in PDAC-derived exosomes, and its blockade prevented liver pre-metastatic niche formation and metastasis. Compared with patients whose pancreatic tumours did not progress, MIF was markedly higher in exosomes from stage I PDAC patients who later developed liver metastasis. These findings suggest that exosomal MIF primes the liver for metastasis and may be a prognostic marker for the development of PDAC liver metastasis.

  7. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. International-journal Peer-reviewed

    Basant Kumar Thakur, Haiying Zhang, Annette Becker, Irina Matei, Yujie Huang, Bruno Costa-Silva, Yan Zheng, Ayuko Hoshino, Helene Brazier, Jenny Xiang, Caitlin Williams, Ruth Rodriguez-Barrueco, Jose M Silva, Weijia Zhang, Stephen Hearn, Olivier Elemento, Navid Paknejad, Katia Manova-Todorova, Karl Welte, Jacqueline Bromberg, Héctor Peinado, David Lyden

    Cell research　24　(6)　766-9　2014/06

    DOI： 10.1038/cr.2014.44 　

    ISSN： 1001-0602

    eISSN： 1748-7838

  8. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. International-journal Peer-reviewed

    Héctor Peinado, Maša Alečković, Simon Lavotshkin, Irina Matei, Bruno Costa-Silva, Gema Moreno-Bueno, Marta Hergueta-Redondo, Caitlin Williams, Guillermo García-Santos, Cyrus Ghajar, Ayuko Nitadori-Hoshino, Caitlin Hoffman, Karen Badal, Benjamin A Garcia, Margaret K Callahan, Jianda Yuan, Vilma R Martins, Johan Skog, Rosandra N Kaplan, Mary S Brady, Jedd D Wolchok, Paul B Chapman, Yibin Kang, Jacqueline Bromberg, David Lyden

    Nature medicine　18　(6)　883-91　2012/06

    DOI： 10.1038/nm.2753 　

    ISSN： 1078-8956

  9. Podoplanin-positive fibroblasts enhance lung adenocarcinoma tumor formation: podoplanin in fibroblast functions for tumor progression. International-journal Peer-reviewed

    Ayuko Hoshino, Genichiro Ishii, Takashi Ito, Kazuhiko Aoyagi, Yoichi Ohtaki, Kanji Nagai, Hiroki Sasaki, Atsushi Ochiai

    Cancer research　71　(14)　4769-79　2011/07/15

    DOI： 10.1158/0008-5472.CAN-10-3228 　

    ISSN： 0008-5472

  10. Human vascular adventitial fibroblasts contain mesenchymal stem/progenitor cells. International-journal Peer-reviewed

    Ayuko Hoshino, Haruki Chiba, Kanji Nagai, Genichiro Ishii, Atsushi Ochiai

    Biochemical and biophysical research communications　368　(2)　305-10　2008/04/04

    DOI： 10.1016/j.bbrc.2008.01.090 　

    ISSN： 0006-291X

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    Vascular adventitia is thought to change functions and contribute to diseases such as atherosclerosis, vascular restenosis, and fibrosis. To determine whether the adventitia contains mesenchymal stem/progenitor cells (MPCs), we cultured human vascular adventitial fibroblasts (hVAFs) from pulmonary arteries and analyzed their characteristics. The doubling time of the hVAFs was 1.5days, and the average number of passage was 11, which was independent of age and sex. The hVAFs were positive for vimentin, collagen type-1, CD29, CD44, and CD105, but negative for hematopoietic and endothelial cell markers. When hVAFs were cultured in appropriate media, they showed osteogenic and adipogenic differentiation by von Kossa, alkaline phosphatase, and oil red O staining. Myogenic differentiation was identified by increased expression of smooth muscle actin and calponin. These findings demonstrate that human vascular adventitia contains MPCs, and that hVAFs may be an ideal source for further experiments on stem cell biology and tissue engineering.

  11. Uptake of small extracellular vesicles by recipient cells is facilitated by paracrine adhesion signaling Peer-reviewed

    Koichiro M. Hirosawa, Yusuke Sato, Rinshi S. Kasai, Eriko Yamaguchi, Naoko Komura, Hiromune Ando, Ayuko Hoshino, Yasunari Yokota, Kenichi G. N. Suzuki

    Nature Communications　16　(1)　2025/03/12

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41467-025-57617-9 　

    eISSN： 2041-1723

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    Abstract Small extracellular vesicles (sEVs) play crucial roles in intercellular communication. However, the internalization of individual sEVs by recipient cells has not been directly observed. Here, we examined these mechanisms using state-of-the-art imaging techniques. Single-molecule imaging shows that tumor-derived sEVs can be classified into several subtypes. Simultaneous single-sEV particle tracking and observation of super-resolution movies of membrane invaginations in living cells reveal that all sEV subtypes are internalized via clathrin-independent endocytosis mediated by galectin-3 and lysosome-associated membrane protein-2C, while some subtypes that recruited raft markers are internalized through caveolae. Integrin β1 and talin-1 accumulate in recipient cell plasma membranes beneath all sEV subtypes. Paracrine, but not autocrine, sEV binding triggers Ca2+ mobilization induced by the activation of Src family kinases and phospholipase Cγ. Subsequent Ca2+-induced activation of calcineurin–dynamin promotes sEV internalization, leading to the recycling pathway. Thus, we clarified the detailed mechanisms of sEV internalization driven by paracrine adhesion signaling.

  12. Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer Peer-reviewed

    Linda Bojmar, Constantinos P. Zambirinis, Jonathan M. Hernandez, Jayasree Chakraborty, Lee Shaashua, Junbum Kim, Kofi Ennu Johnson, Samer Hanna, Gokce Askan, Jonas Burman, Hiranmayi Ravichandran, Jian Zheng, Joshua S. Jolissaint, Rami Srouji, Yi Song, Ankur Choubey, Han Sang Kim, Michele Cioffi, Elke van Beek, Carlie Sigel, Jose Jessurun, Paulina Velasco Riestra, Hakon Blomstrand, Carolin Jönsson, Anette Jönsson, Pernille Lauritzen, Weston Buehring, Yonathan Ararso, Dylanne Hernandez, Jessica P. Vinagolu-Baur, Madison Friedman, Caroline Glidden, Laetitia Firmenich, Grace Lieberman, Dianna L. Mejia, Naaz Nasar, Anders P. Mutvei, Doru M. Paul, Yaron Bram, Bruno Costa-Silva, Olca Basturk, Nancy Boudreau, Haiying Zhang, Irina R. Matei, Ayuko Hoshino, David Kelsen, Irit Sagi, Avigdor Scherz, Ruth Scherz-Shouval, Yosef Yarden, Moshe Oren, Mikala Egeblad, Jason S. Lewis, Kayvan Keshari, Paul M. Grandgenett, Michael A. Hollingsworth, Vinagolu K. Rajasekhar, John H. Healey, Bergthor Björnsson, Diane M. Simeone, David A. Tuveson, Christine A. Iacobuzio-Donahue, Jaqueline Bromberg, C. Theresa Vincent, Eileen M. O’Reilly, Ronald P. DeMatteo, Vinod P. Balachandran, Michael I. D’Angelica, T. Peter Kingham, Peter J. Allen, Amber L. Simpson, Olivier Elemento, Per Sandström, Robert E. Schwartz, William R. Jarnagin, David Lyden

    Nature Medicine　30　(8)　2170-2180　2024/06/28

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41591-024-03075-7 　

    ISSN： 1078-8956

    eISSN： 1546-170X

  13. Protocol for cross-platform characterization of human and murine extracellular vesicles and particles Peer-reviewed

    Linda Bojmar, Han Sang Kim, Kei Sugiura, Søren Heissel, Serena Lucotti, Michele Cioffi, Kofi Ennu Johnson, Leona Cohen-Gould, Haiying Zhang, Henrik Molina, Irina R. Matei, David Lyden, Ayuko Hoshino

    STAR Protocols　5　(1)　102754-102754　2024/03

    Publisher: Elsevier BV

    DOI： 10.1016/j.xpro.2023.102754 　

    ISSN： 2666-1667

  14. Advancement in Cellular Topographic and Nanoparticle Capture Imaging by High Resolution Microscopy Incorporating a Freeze-Drying and Gaseous Nitrogen-based Approach Peer-reviewed

    Kunihiro Uryu, Nadine Soplop, Timothy P. Sheahan, Maria-Teresa Catanese, Chuong Huynh, John Pena, Nancy Boudreau, Irina Matei, Candia Kenific, Ayako Hashimoto, Ayuko Hoshino, Charles M. Rice, David Lyden

    2023/09/28

    Publisher: Cold Spring Harbor Laboratory

    DOI： 10.1101/2023.09.28.559906 　

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    Abstract Scanning electron microscopy (SEM) offers an unparalleled view of the membrane topography of mammalian cells by using a conventional osmium (OsO4) and ethanol-based tissue preparation. However, conventional SEM methods limit optimal resolution due to ethanol and lipid interactions and interfere with visualization of fluorescent reporter proteins. Therefore, SEM correlative light and electron microscopy (CLEM) has been hindered by the adverse effects of ethanol and OsO4on retention of fluorescence signals. To overcome this technological gap in achieving high-resolution SEM and retain fluorescent reporter signals, we developed a freeze-drying method with gaseous nitrogen (FDGN). We demonstrate that FDGN preserves cyto-architecture to allow visualization of detailed membrane topography while retaining fluorescent signals and that FDGN processing can be used in conjunction with a variety of high-resolution imaging systems to enable collection and validation of unique, high-quality data from these approaches. In particular, we show that FDGN coupled with high resolution microscopy provided detailed insight into viral or tumor-derived extracellular vesicle (TEV)-host cell interactions and may aid in designing new approaches to intervene during viral infection or to harness TEVs as therapeutic agents.

  15. GeLC-FAIMS-MS workflow for in-depth middle-down proteomics. International-journal Peer-reviewed

    Ayako Takemori, Philipp T Kaulich, Ryo Konno, Yusuke Kawashima, Yuto Hamazaki, Ayuko Hoshino, Andreas Tholey, Nobuaki Takemori

    Proteomics　e2200431　2023/08/07

    DOI： 10.1002/pmic.202200431 　

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    Middle-down proteomics (MDP) is an analytical approach in which protein samples are digested with proteases such as Glu-C to generate large peptides (>3 kDa) that are analyzed by mass spectrometry (MS). This method is useful for characterizing high-molecular-weight proteins that are difficult to detect by top-down proteomics (TDP), in which intact proteins are analyzed by MS. In this study, we applied GeLC-FAIMS-MS, a multidimensional separation workflow that combines gel-based prefractionation with LC-FAIMS MS, for deep MDP. Middle-down peptides generated by optimized limited Glu-C digestion conditions were first size-fractionated by polyacrylamide gel electrophoresis, followed by C4 reversed-phase liquid chromatography separation and additional ion mobility fractionation, resulting in a significant increase in peptide length detectable by MS. In addition to global analysis, the GeLC-FAIMS-MS concept can also be applied to targeted MDP, where only proteins in the desired molecular weight range are gel-fractionated and their Glu-C digestion products are analyzed, as demonstrated by targeted analysis of integrins in exosomes. In-depth MDP achieved by global and targeted GeLC-FAIMS-MS supports the exploration of proteoform information not covered by conventional TDP by increasing the number of detectable protein groups or post-translational modifications (PTMs) and improving the sequence coverage.

  16. Needle-Type Pressure Sensor with Silicone Oil and Parylene Membrane inside for Minimally Invasive Measurement Peer-reviewed

    Takuto Kishimoto, Masakazu Agetsuma, Ayuko Hoshino, Hidetoshi Takahashi

    IEEJ Transactions on Sensors and Micromachines　143　(7)　148-155　2023/07/01

    Publisher: Institute of Electrical Engineers of Japan (IEE Japan)

    DOI： 10.1541/ieejsmas.143.148 　

    ISSN： 1341-8939

    eISSN： 1347-5525

  17. A peptide binding to the tetraspanin CD9 reduces cancer metastasis. International-journal Peer-reviewed

    Thanawat Suwatthanarak, Kazuma Ito, Masayoshi Tanaka, Kei Sugiura, Ayuko Hoshino, Yoshitaka Miyamoto, Kenji Miyado, Mina Okochi

    Biomaterials advances　146　213283-213283　2023/03

    DOI： 10.1016/j.bioadv.2023.213283 　

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    As an organizer of multi-molecular membrane complexes, the tetraspanin CD9 has been implicated in a number of biological processes, including cancer metastasis, and is a candidate therapeutic target. Here, we evaluated the suppressive effects of an eight-mer CD9-binding peptide (CD9-BP) on cancer cell metastasis and its mechanisms of action. CD9-BP impaired CD9-related functions by adversely affecting the formation of tetraspanin webs-networks composed of CD9 and its partner proteins. The anti-cancer metastasis effect of CD9-BP was evidenced by the in vitro inhibition of cancer cell migration and invasion as well as exosome secretion and uptake, which are essential processes during metastasis. Finally, using a mouse model, we showed that CD9-BP reduced lung metastasis in vivo. These findings provide insight into the mechanism by which CD9-BP inhibits CD9-dependent functions and highlight its potential application as an alternative therapeutic nano-biomaterial for metastatic cancers.

  18. Freeing up Japan's PhD potential. International-journal

    Ayuko Hoshino

    Nature　615　(7951)　S57　2023/03

    DOI： 10.1038/d41586-023-00659-0 　

  19. Protocol for Plasma Extracellular Vesicle and Particle Isolation and Mass Spectrometry-Based Proteomic Identification. International-journal Peer-reviewed

    Amirmohammad Nasiri Kenari, Linda Bojmar, Søren Heissel, Henrik Molina, David Lyden, Ayuko Hoshino

    Methods in molecular biology (Clifton, N.J.)　2628　291-300　2023

    DOI： 10.1007/978-1-0716-2978-9_19 　

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    Plasma extracellular vesicles and particles (EVPs) are enriched in biomolecules that reflect individuals' physiological and pathological states. Several studies have demonstrated the potential of human plasma EVPs as a novel liquid biopsy. Here we describe a protocol for human plasma EVPs isolation and proteomic characterization. We isolated human plasma EVPs by the classical ultracentrifugation method and performed mass spectrometry-based proteomic profiling. Using this protocol, researchers can reveal the plasma EVPs proteome and explore the clinical application of plasma EVPs proteins for developing disease biomarkers.

  20. Metastasis suppressor NME1 in exosomes or liposomes conveys motility and migration inhibition in breast cancer model systems. International-journal Peer-reviewed

    Imran Khan, Brunilde Gril, Ayuko Hoshino, Howard H Yang, Maxwell P Lee, Simone Difilippantonio, David C Lyden, Patricia S Steeg

    Clinical & experimental metastasis　39　(5)　815-831　2022/10

    DOI： 10.1007/s10585-022-10182-7 　

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    Tumor-derived exosomes have documented roles in accelerating the initiation and outgrowth of metastases, as well as in therapy resistance. Little information supports the converse, that exosomes or similar vesicles can suppress metastasis. We investigated the NME1 (Nm23-H1) metastasis suppressor as a candidate for metastasis suppression by extracellular vesicles. Exosomes derived from two cancer cell lines (MDA-MB-231T and MDA-MB-435), when transfected with the NME1 (Nm23-H1) metastasis suppressor, secreted exosomes with NME1 as the predominant constituent. These exosomes entered recipient tumor cells, altered their endocytic patterns in agreement with NME1 function, and suppressed in vitro tumor cell motility and migration compared to exosomes from control transfectants. Proteomic analysis of exosomes revealed multiple differentially expressed proteins that could exert biological functions. Therefore, we also prepared and investigated liposomes, empty or containing partially purified rNME1. rNME1 containing liposomes recapitulated the effects of exosomes from NME1 transfectants in vitro. In an experimental lung metastasis assay the median lung metastases per histologic section was 158 using control liposomes and 15 in the rNME1 liposome group, 90.5% lower than the control liposome group (P = 0.016). The data expand the exosome/liposome field to include metastasis suppressive functions and describe a new translational approach to prevent metastasis.

  21. [Exosome, a Nano-Sized Carrier, and the Brain-Gut Correlation]. Peer-reviewed

    Kei Sugiura, Hinako Shimura, Ayuko Hoshino

    Brain and nerve = Shinkei kenkyu no shinpo　73　(8)　879-887　2021/08

    DOI： 10.11477/mf.1416201855 　

    More details Close

    Exosomes, small bilayer vesicles secreted by all cells, are recognized as a novel communication tool among distant organs. They can cross the blood-brain barrier and be taken up by specific brain cells, altering the brain microenvironment and possibly playing a role in pathological conditions such as brain metastasis and neurodegenerative diseases. Intestinal bacteria also release small membrane vesicles called "bacterial extracellular vesicles" (BEVs), which can invade blood vessels and affect distant tissues in a manner similar to exosomes, suggesting that BEVs also play a role in disease progression in the brain-gut axis. Here, we will discuss the latest findings of the relationship between exosomes, including BEVs, and multiple brain pathologies.

  22. Extracellular vesicle and particle isolation from human and murine cell lines, tissues, and bodily fluids. International-journal Peer-reviewed

    Linda Bojmar, Han Sang Kim, Gabriel C Tobias, Fanny A Pelissier Vatter, Serena Lucotti, Kofi Ennu Gyan, Candia M Kenific, Zurong Wan, Kyung-A Kim, DooA Kim, Jonathan Hernandez, Virginia Pascual, Todd E Heaton, Michael P La Quaglia, David Kelsen, Tanya M Trippett, David R Jones, William R Jarnagin, Irina R Matei, Haiying Zhang, Ayuko Hoshino, David Lyden

    STAR protocols　2　(1)　100225-100225　2021/03/19

    DOI： 10.1016/j.xpro.2020.100225 　

    More details Close

    We developed a modified protocol, based on differential ultracentrifugation (dUC), to isolate extracellular vesicles and particles (specifically exomeres) (EVPs) from various human and murine sources, including cell lines, surgically resected tumors and adjacent tissues, and bodily fluids, such as blood, lymphatic fluid, and bile. The diversity of these samples requires robust and highly reproducible protocols and refined isolation technology, such as asymmetric-flow field-flow fractionation (AF4). Our isolation protocol allows for preparation of EVPs for various downstream applications, including proteomic profiling. For complete details on the use and execution of this protocol, please refer to Hoshino et al. (2020).

  23. Impact of exosome-mediated feto-maternal interactions on pregnancy maintenance and development of obstetric complications. International-journal Peer-reviewed

    Ayako Hashimoto, Kei Sugiura, Ayuko Hoshino

    Journal of biochemistry　169　(2)　163-171　2021/03/05

    DOI： 10.1093/jb/mvaa137 　

    More details Close

    Pregnancy is an immunological paradox, a phenomenon in which the foetus and the placenta, containing foreign antigens to the mother, develop without inducing rejection by the maternal immune system. Cell-to-cell communication between the foetus and the mother is mediated by secreted factors such as cytokines, hormones and extracellular vesicles (EVs) for a successful pregnancy and to avoid rejection. Exosomes, the smallest of EVs, are released extracellularly, where they are taken up by proximal or distant recipient cells. Here, we discuss the role of EVs, especially exosomes in feto-maternal communication during pregnancy. This review will provide an overview of the functional roles exosomes may play during embryo implantation, modulating immune responses during pregnancy and the onset of labour. Moreover, we will discuss exosomal function in obstetric pathology, and the development of pregnancy-associated complications such as preeclampsia and preterm birth as well as the biomarker potential of exosomes for detecting such conditions.

  24. Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers. International-journal Peer-reviewed

    Ayuko Hoshino, Han Sang Kim, Linda Bojmar, Kofi Ennu Gyan, Michele Cioffi, Jonathan Hernandez, Constantinos P Zambirinis, Gonçalo Rodrigues, Henrik Molina, Søren Heissel, Milica Tesic Mark, Loïc Steiner, Alberto Benito-Martin, Serena Lucotti, Angela Di Giannatale, Katharine Offer, Miho Nakajima, Caitlin Williams, Laura Nogués, Fanny A Pelissier Vatter, Ayako Hashimoto, Alexander E Davies, Daniela Freitas, Candia M Kenific, Yonathan Ararso, Weston Buehring, Pernille Lauritzen, Yusuke Ogitani, Kei Sugiura, Naoko Takahashi, Maša Alečković, Kayleen A Bailey, Joshua S Jolissant, Huajuan Wang, Ashton Harris, L Miles Schaeffer, Guillermo García-Santos, Zoe Posner, Vinod P Balachandran, Yasmin Khakoo, G Praveen Raju, Avigdor Scherz, Irit Sagi, Ruth Scherz-Shouval, Yosef Yarden, Moshe Oren, Mahathi Malladi, Mary Petriccione, Kevin C De Braganca, Maria Donzelli, Cheryl Fischer, Stephanie Vitolano, Geraldine P Wright, Lee Ganshaw, Mariel Marrano, Amina Ahmed, Joe DeStefano, Enrico Danzer, Michael H A Roehrl, Norman J Lacayo, Theresa C Vincent, Martin R Weiser, Mary S Brady, Paul A Meyers, Leonard H Wexler, Srikanth R Ambati, Alexander J Chou, Emily K Slotkin, Shakeel Modak, Stephen S Roberts, Ellen M Basu, Daniel Diolaiti, Benjamin A Krantz, Fatima Cardoso, Amber L Simpson, Michael Berger, Charles M Rudin, Diane M Simeone, Maneesh Jain, Cyrus M Ghajar, Surinder K Batra, Ben Z Stanger, Jack Bui, Kristy A Brown, Vinagolu K Rajasekhar, John H Healey, Maria de Sousa, Kim Kramer, Sujit Sheth, Jeanine Baisch, Virginia Pascual, Todd E Heaton, Michael P La Quaglia, David J Pisapia, Robert Schwartz, Haiying Zhang, Yuan Liu, Arti Shukla, Laurence Blavier, Yves A DeClerck, Mark LaBarge, Mina J Bissell, Thomas C Caffrey, Paul M Grandgenett, Michael A Hollingsworth, Jacqueline Bromberg, Bruno Costa-Silva, Hector Peinado, Yibin Kang, Benjamin A Garcia, Eileen M O'Reilly, David Kelsen, Tanya M Trippett, David R Jones, Irina R Matei, William R Jarnagin, David Lyden

    Cell　182　(4)　1044-1061　2020/08/20

    DOI： 10.1016/j.cell.2020.07.009 　

    More details Close

    There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n = 151) and plasma-derived (n = 120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer. Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.

  25. Ribosome biogenesis during cell cycle arrest fuels EMT in development and disease. International-journal Peer-reviewed

    Varsha Prakash, Brittany B Carson, Jennifer M Feenstra, Randall A Dass, Petra Sekyrova, Ayuko Hoshino, Julian Petersen, Yuan Guo, Matthew M Parks, Chad M Kurylo, Jake E Batchelder, Kristian Haller, Ayako Hashimoto, Helene Rundqivst, John S Condeelis, C David Allis, Denis Drygin, M Angela Nieto, Michael Andäng, Piergiorgio Percipalle, Jonas Bergh, Igor Adameyko, Ann-Kristin Östlund Farrants, Johan Hartman, David Lyden, Kristian Pietras, Scott C Blanchard, C Theresa Vincent

    Nature communications　10　(1)　2110-2110　2019/05/08

    DOI： 10.1038/s41467-019-10100-8 　

    More details Close

    Ribosome biogenesis is a canonical hallmark of cell growth and proliferation. Here we show that execution of Epithelial-to-Mesenchymal Transition (EMT), a migratory cellular program associated with development and tumor metastasis, is fueled by upregulation of ribosome biogenesis during G1/S arrest. This unexpected EMT feature is independent of species and initiating signal, and is accompanied by release of the repressive nucleolar chromatin remodeling complex (NoRC) from rDNA, together with recruitment of the EMT-driving transcription factor Snai1 (Snail1), RNA Polymerase I (Pol I) and the Upstream Binding Factor (UBF). EMT-associated ribosome biogenesis is also coincident with increased nucleolar recruitment of Rictor, an essential component of the EMT-promoting mammalian target of rapamycin complex 2 (mTORC2). Inhibition of rRNA synthesis in vivo differentiates primary tumors to a benign, Estrogen Receptor-alpha (ERα) positive, Rictor-negative phenotype and reduces metastasis. These findings implicate the EMT-associated ribosome biogenesis program with cellular plasticity, de-differentiation, cancer progression and metastatic disease.

  26. Complex polymorphisms in endocytosis genes suggest alpha-cyclodextrin as a treatment for breast cancer. International-journal Peer-reviewed

    Wittkowski KM, Dadurian C, Seybold MP, Kim HS, Hoshino A, Lyden D

    PloS one　13　(7)　e0199012　2018

    DOI： 10.1371/journal.pone.0199012 　

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    Most breast cancer deaths are caused by metastasis and treatment options beyond radiation and cytotoxic drugs, which have severe side effects, and hormonal treatments, which are or become ineffective for many patients, are urgently needed. This study reanalyzed existing data from three genome-wide association studies (GWAS) using a novel computational biostatistics approach (muGWAS), which had been validated in studies of 600-2000 subjects in epilepsy and autism. MuGWAS jointly analyzes several neighboring single nucleotide polymorphisms while incorporating knowledge about genetics of heritable diseases into the statistical method and about GWAS into the rules for determining adaptive genome-wide significance. Results from three independent GWAS of 1000-2000 subjects each, which were made available under the National Institute of Health's "Up For A Challenge" (U4C) project, not only confirmed cell-cycle control and receptor/AKT signaling, but, for the first time in breast cancer GWAS, also consistently identified many genes involved in endo-/exocytosis (EEC), most of which had already been observed in functional and expression studies of breast cancer. In particular, the findings include genes that translocate (ATP8A1, ATP8B1, ANO4, ABCA1) and metabolize (AGPAT3, AGPAT4, DGKQ, LPPR1) phospholipids entering the phosphatidylinositol cycle, which controls EEC. These novel findings suggest scavenging phospholipids as a novel intervention to control local spread of cancer, packaging of exosomes (which prepare distant microenvironment for organ-specific metastases), and endocytosis of β1 integrins (which are required for spread of metastatic phenotype and mesenchymal migration of tumor cells). Beta-cyclodextrins (βCD) have already been shown to be effective in in vitro and animal studies of breast cancer, but exhibits cholesterol-related ototoxicity. The smaller alpha-cyclodextrins (αCD) also scavenges phospholipids, but cannot fit cholesterol. An in-vitro study presented here confirms hydroxypropyl (HP)-αCD to be twice as effective as HPβCD against migration of human cells of both receptor negative and estrogen-receptor positive breast cancer. If the previous successful animal studies with βCDs are replicated with the safer and more effective αCDs, clinical trials of adjuvant treatment with αCDs are warranted. Ultimately, all breast cancer are expected to benefit from treatment with HPαCD, but women with triple-negative breast cancer (TNBC) will benefit most, because they have fewer treatment options and their cancer advances more aggressively.

  27. Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer. International-journal Peer-reviewed

    Pasquale Sansone, Claudia Savini, Ivana Kurelac, Qing Chang, Laura Benedetta Amato, Antonio Strillacci, Anna Stepanova, Luisa Iommarini, Chiara Mastroleo, Laura Daly, Alexander Galkin, Basant Kumar Thakur, Nadine Soplop, Kunihiro Uryu, Ayuko Hoshino, Larry Norton, Massimiliano Bonafé, Monica Cricca, Giuseppe Gasparre, David Lyden, Jacqueline Bromberg

    Proceedings of the National Academy of Sciences of the United States of America　114　(43)　E9066-E9075-E10255　2017/10/24

    DOI： 10.1073/pnas.1704862114 　

    ISSN： 0027-8424

  28. The Effect of Cage Shape on Nanoparticle-Based Drug Carriers: Anticancer Drug Release and Efficacy via Receptor Blockade Using Dextran-Coated Iron Oxide Nanocages. International-journal Peer-reviewed

    Sham Rampersaud, Justin Fang, Zengyan Wei, Kristina Fabijanic, Stefan Silver, Trisha Jaikaran, Yuleisy Ruiz, Murielle Houssou, Zhiwei Yin, Shengping Zheng, Ayako Hashimoto, Ayuko Hoshino, David Lyden, Shahana Mahajan, Hiroshi Matsui

    Nano letters　16　(12)　7357-7363　2016/12/14

    DOI： 10.1021/acs.nanolett.6b02577 　

    ISSN： 1530-6984

    eISSN： 1530-6992

  29. Morphophenotype of floating colonies derived from a single cancer cell has a critical impact on tumor-forming activity. International-journal Peer-reviewed

    Genichiro Ishii, Hiroko Hashimoto, Naho Atsumi, Ayuko Hoshino, Atsushi Ochiai

    Pathology international　63　(1)　29-36　2013/01

    DOI： 10.1111/pin.12018 　

    ISSN： 1320-5463

    More details Close

    The anchorage-independent colony growth of cancer cells is reportedly correlated with the tumor-forming activity; however, the correlation between the morphophenotype of each colony and the tumor-forming activity has not been clarified. To assess this problem, we cultured single A549 cells (human lung adenocarcinoma cell line) in growth medium in individual wells (n = 426) for 14 days under anchorage-independent conditions and analyzed the resulting growth characteristics. The single A549 cells formed various sizes of floating colonies. The proportion of large colonies (>400 μm) was 3.8% and this proportion increased dramatically with the exogenous addition of EGF (21.6%) or HGF (27.6%). Morphologically, the floating colonies could be divided into: (ii) Type A, spheroid colony; and (ii) Type B, dispersed villous colony. The Type B colonies expressed significantly higher levels of epithelial-mesenchymal transition (EMT)-related mRNAs (Snail 1, ZEB 1, and ZEB2) than the Type A colonies. Furthermore, the subcutaneous injection of a single cell-derived colony with a large size and a Type B morphology resulted in more efficient tumor formation. The present results indicated that the morphophenotypes of floating colonies derived from single cancer cells have a critical impact on tumor-forming activity.

  30. Tumor promoting effect of podoplanin-positive fibroblasts is mediated by enhanced RhoA activity. International-journal Peer-reviewed

    Suguru Ito, Genichiro Ishii, Ayuko Hoshino, Hiroko Hashimoto, Shinya Neri, Takeshi Kuwata, Morihiro Higashi, Kanji Nagai, Atsushi Ochiai

    Biochemical and biophysical research communications　422　(1)　194-9　2012/05/25

    DOI： 10.1016/j.bbrc.2012.04.158 　

    ISSN： 0006-291X

  31. Fibroblasts associated with cancer cells keep enhanced migration activity after separation from cancer cells: a novel character of tumor educated fibroblasts. International-journal Peer-reviewed

    Genichiro Ishii, Hiroko Hashimoto, Kiyoshi Asada, Takashi Ito, Ayuko Hoshino, Satoshi Fujii, Motohiro Kojima, Takeshi Kuwata, Kenichi Harigaya, Kanji Nagai, Toshikazu Ushijima, Atsushi Ochiai

    International journal of oncology　37　(2)　317-25　2010/08

    DOI： 10.3892/ijo-0000680 　

    ISSN： 1019-6439

    eISSN： 1791-2423

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    It is now clear that the association between cancer cells and recruited fibroblasts (cancer-associated fibroblasts; CAFs) leads to alteration of the biological properties of both types of cells and creates a specific microenvironment. Here we report a novel biological property of CAFs and its cellular mechanism using in vivo and in vitro model. Cultured CAFs derived from human lung cancer tissue displayed significantly higher migration activity in response to PDGF-BB than that of fibroblasts from corresponding non-cancerous tissue (NCAFs). Moreover, KM104GFP (GFP-labeled human fibroblast cell line) co-cultured with human cancer cell line Capan-1 showed significantly higher migration activity than KM104GFP alone. No such phenomenon occurred when KM104GFP and Capan-1 were cultured separately. Even after KM104GFP were sorted from co-cultured Capan-1, KM104GFP retained their enhanced migration activity until passage-5 of culture in the absence of cancer cells. Despite a similar level of phosphorylation of ERK1/2 after exposure to PDGF-BB, the inhibitory effect of MEK inhibitor was significantly higher on migration of KM104GFP that had been sorted from co-cultured Capan-1 than of KM104GFP alone. This higher dependence on ERK1/2 signaling for cell migration was also seen in CAFs obtained from cancer tissue. The results of this study indicate that by association with cancer cells, CAFs can acquire enhanced migration activity which could be kept after separation from cancer cells and suggest the possibility that higher dependence on ERK1/2 signaling for enhanced migration activity would be one of the biological properties of CAFs.

  32. Degradation of soluble VEGF receptor-1 by MMP-7 allows VEGF access to endothelial cells. International-journal Peer-reviewed

    Ta-Kashi Ito, Genichiro Ishii, Seiji Saito, Keiichi Yano, Ayuko Hoshino, Tasuku Suzuki, Atsushi Ochiai

    Blood　113　(10)　2363-9　2009/03/05

    DOI： 10.1182/blood-2008-08-172742 　

    ISSN： 0006-4971

    More details Close

    Vascular endothelial growth factor (VEGF) signaling in endothelial cells serves a critical role in physiologic and pathologic angiogenesis. Endothelial cells secrete soluble VEGF receptor-1 (sVEGFR-1/sFlt-1), an endogenous VEGF inhibitor that sequesters VEGF and blocks its access to VEGF receptors. This raises the question of how VEGF passes through this endogenous VEGF trap to reach its membrane receptors on endothelial cells, a step required for VEGF-driven angiogenesis. Here, we show that matrix metalloproteinase-7 (MMP-7) degrades human sVEGFR-1, which increases VEGF bioavailability around the endothelial cells. Using a tube formation assay, migration assay, and coimmunoprecipitation assay with human umbilical vein endothelial cells (HUVECs), we show that the degradation of sVEGFR-1 by MMP-7 liberates the VEGF(165) isoform from sVEGFR-1. The presence of MMP-7 abrogates the inhibitory effect of sVEGFR-1 on VEGF-induced phosphorylation of VEGF receptor-2 on HUVECs. These data suggest that VEGF escapes the sequestration by endothelial sVEGFR-1 and promotes angiogenesis in the presence of MMP-7.

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Misc. 8

  1. TUMOR-DERIVED EXOSOMES PROMOTE ORGANOTROPIC METASTASIS AND SYSTEMIC DISEASE

    HOSHINO Ayuko, HASHIMOTO Ayako, ZHANG Haiying, LYDEN David

    Extended Abstracts for the International Symposium of the Princess Takamatsu Cancer Research Fund　48th　16‐20　2018

    ISSN： 2186-8603

  2. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET (vol 18, pg 883, 2012)

    Hector Peinado, Masa Alec Kovic, Simon Lavotshkin, Irina Matei, Bruno Costa-Silva, Gema Moreno-Bueno, Marta Hergueta-Redondo, Caitlin Williams, Guillermo Garcia-Santos, Cyrus M. Ghajar, Ayuko Nitadori-Hoshino, Caitlin Hoffman, Karen Badal, Benjamin A. Garcia, Margaret K. Callahan, Jianda Yuan, Vilma R. Martins, Johan Skog, Rosandra N. Kaplan, Mary S. Brady, Jedd D. Wolchok, Paul B. Chapman, Yibin Kang, Jacqueline Bromberg, David Lyden

    NATURE MEDICINE　22　(12)　1502-1502　2016/12

    ISSN： 1078-8956

    eISSN： 1546-170X

  3. Tumor-derived exosomes initiate pre-metastatic niche formation and organotropism

    Ayuko Hoshino, Bruno Costa Da Silva, Tang-Long Shen, Goncalo Rodrigues, Masa Aleckovic, Yibin Kang, Hector Peinado, Jacqueline Bromberg, David Lyden

    CLINICAL & EXPERIMENTAL METASTASIS　32　(3)　185-185　2015/03

    ISSN： 0262-0898

    eISSN： 1573-7276

  4. がん細胞由来エクソソームに発現するインテグリンががん転移先を決定する

    HOSHINO Ayuko, COSTA‐SILVA Bruno, HASHIMOTO Ayako, PEINADO Hector, BROMBERG Jacqueline, LYDEN David

    日本生化学会大会(Web)　88th　2LBA099 (WEB ONLY)　2015

  5. Biological roles of cancer stromal cells on cancer progression

    OCHIAI Atsushi, HOSHINO Ayuko, ISHII Genichiro

    日本癌学会学術総会記事　69th　402　2010/08/23

  6. Podoplanin Positive Cells in Human Vascular Adventitial Fibroblasts promote Tumor Formation

    HOSHINO Ayuko, ISHII Genichiro, OCHIAI Atsushi

    日本癌学会学術総会記事　68th　210　2009/08/31

  7. Characteristics of Human Pulmonary Vascular Adventitia

    HOSHINO Ayuko, OCHIAI Atsushi, ISHII Genichiro

    日本癌学会学術総会記事　66th　197　2007/08/25

  8. Study on the relationship of angiogenesis and fibrinolysis using the perfusion cell culture system

    HAYASHI Moyuru, HOSHINO Ayuko, MATSUZAKI Yuichi, SHIMONAKA Motoyuki

    生化学　77　(8)　848　2005/08/25

    ISSN： 0037-1017

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Books and Other Publications 12

  1. 人体の細胞生物学 : カラー図解 = Human cell biology : an introduction for medical students

    坂井, 建雄, 石崎, 泰樹

    日本医事新報社　2025/01

    ISBN: 9784784932337

  2. 実験医学別冊 「留学する？」から一歩踏み出す研究留学実践ガイド 人生の選択肢を広げよう

    星野歩子

    2024/09/20

    ISBN: 9784758122733

  3. 脳神経内科 (第101巻第1号/2024年7月発行）

    志村日向子, 加藤真未, 星野 歩子

    科学評論社　2024/07/25

  4. 良い炎症・悪い炎症から捉え直すがんと免疫 : 慢性感染、肥満、老化などによる慢性炎症を制御し、がんの予防と新規治療をめざす

    星野歩子

    羊土社　2024/06/05

    ISBN: 9784758104197

  5. Medical Science Digest 2023年9月号 リキッドバイオプシーによるがん先端研究

    前本 道寛, 星野 歩子

    ニュー・サイエンス社　2023/08/31

  6. 生化学(Vol.95 No.3 2023)

    正古 悠一, 小川 瑶葉, 星野 歩子

    公益社団法人日本生化学会　2023/06/05

  7. 感染･炎症･免疫(VOL.52 NO.2 2022 Autumn)

    本城 麻衣, 正古 悠一, 星野 歩子

    鳥居薬品(株)　2022/10/15

  8. パラダイムシフトをもたらすエクソソーム機能研究最前線

    星野 歩子

    エヌ・ティー・エス　2017

  9. がん細胞由来エクソソームに発現するインテグリンによる臓器特異性転移

    星野 歩子

    がん分子標的治療　2017

  10. 転移形成におけるExosomeの役割

    星野 歩子

    肝胆膵　2017

  11. 転移先を決める接着分子

    星野 歩子

    医学のあゆみ　2016

  12. エクソソームによるがん転移の新しいストーリー

    星野 歩子

    実験医学　2016

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Presentations 33

  1. 腫瘍関連エクソソームのプロテオミクスから解析するがん転移機構と診断バイオマーカー Invited

    星野歩子

    第40回前立腺シンポジウム　2025/12/13

  2. エクソソーム由来分子シグネチャーに基づくASDの診断マーカー探索と病態解析 Invited

    星野歩子

    第48回日本分子生物学会年会　2025/12/03

  3. 母胎連関エクソソーム：エクソソーム解析から見える疾患生物学 Invited

    星野歩子

    第33回日本胎盤学会学術集会・第43回日本絨毛性疾患研究会　2025/11/08

  4. がん細胞産生エクソソームから解読するがん進展機構 Invited

    星野歩子

    第84回日本癌学会学術総会　2025/09/27

  5. エクソソーム解析から目指す;自閉スペクトラム症の新たな病態解明 Invited

    星野歩子

    千里ライフサイエンスセミナー X2 脳免疫の生理から病理まで　2025/07/09

  6. Systemic communication via;exosomes in cancer;Integrating tumor signatures, aging;pre-metastatic niche formation Invited

    Ayuko Hoshino

    The 43rd Sapporo International Cancer Symposium　2025/07/06

  7. エクソソーム解析からみる疾患生物学 Invited

    星野歩子

    第89回 日本生化学会中部支部例会・シンポジウム　2025/05/24

  8. Exosomes: From Cellular Waste to Disease Biomarkers Invited

    Towards the Future of Communication: Creating an Inclusive World with Neuro/Bioscience and Engineering Technologies　2025/03/28

  9. 臓器間コミュニケーションを担うエクソソームの役割と疾患進展機構の解明 Invited

    星野歩子

    血管生物特別集会　2025/02/22

  10. エクソソーム解析から探る臓器間コミュニケーションと体内状態 Invited

    星野歩子

    第17回 CBIR/ONSA大学院セミナー 若手インスパイアシンポジウム　2025/02/20

  11. Molecular Signals in Autism Spectrum Disorder: Exosome Analysis for Novel Insights Invited

    19th JCAR in Sendai　2025/02/08

  12. 癌転移・進展に関するエクソソームの役割 Invited

    星野歩子

    Scientific Exchange Meeting in Urothelial Cancer 2024　2024/12/20

  13. Exosomes: Drivers in disease progression and biomarker discovery Invited

    Hoshino Ayuko

    2024/10/22

  14. エクソソーム上ITGβ１が司るがん進展機構の解明 Invited

    星野歩子

    竹中奨励賞受賞講演　2024/10/12

  15. Deciphering disease mechanisms and biomarker identification via exosome analysis Invited

    Ayuko Hoshino

    the US-Japan Conference on Cancer Research “Moonshot - the Future of Cancer Prevention”.　2024/09/06

  16. がん転移:がん進行・転移におけるエクソソームの機能 Invited

    星野歩子

    GU Medical Seminar in 2024　2024/08/23

  17. Exosomal analysis of brain-linked disorders Invited

    2024/07/25

  18. 疾患や生理現象に関わるエクソソーム解析 Invited

    星野歩子

    第45回 日本炎症再生医学会　2024/07/17

  19. Deciphering disease mechanisms and biomarker identification via exosome analysis Invited

    Ayuko Hoshino

    Biennial Metastasis Research Conference 2024 London　2024/06/25

  20. Exosomal protein-mediated inter-organ communication: roles in disease etiology and biomarker potential Invited

    2024/05/24

  21. 疾患関連エクソソームによる病態寄与機構と診断マーカー Invited

    星野歩子

    第61回日本放射線腫瘍学会生物部会学術大会、第52回放射線による制癌シンポジウム　2024/05/17

  22. Unlocking the Potential of Exosomes: Understanding Disease Mechanisms and Biomarker Identification Invited

    Ayuko Hoshino

    Serendipity Symposium 2023/2024　2024/03/13

  23. エクソソームからみる生体情報と疾患生物学 Invited

    星野歩子

    【慶應医学会】第102回シンポジウム　2023/11/25

  24. エクソソームを介したがん転移機構：エクソソームによるがん微小環境変化と診断マーカー Invited

    星野歩子

    （公財）実験動物中央研究所（CIEA）主催in vivo実験医学シンポジウム　2023/11/16

  25. Organotropic localization of disease-associated exosomes and its role in etiology Invited

    2023/11/15

  26. Exosomal protein-mediated inter-organ communication : roles in disease etiology and biomarker potential Invited

    Ayuko Hoshino

    KSMCB2023　2023/11/06

  27. Role of exosomes in cancer metastasis and biomarker potential Invited

    2023/09/23

  28. Understanding the roles of exosomes in theprogression and detection of disease Invited

    2023/08/02

  29. エクソソーム含有タンパク質から解析する病態進行機構と診断マーカー Invited

    星野歩子

    第 39 回日本DDS学会学術集会　2023/07/27

  30. エクソソームが切り拓く疾患生物学：病態寄与機構と診断マーカーの解析 Invited

    星野歩子

    LINK-J シンポジウム「創薬のフロンティア」　2023/07/04

  31. エクソソームを介した細胞間コミュニケーション： 病態寄与機構とバイオマーカー解析 Invited

    星野歩子

    第75回日本細胞生物学会大会 シンポジウム　2023/06/29

  32. エクソソームが切り拓く疾患生物学 ～病態機序の可視化が導く診断・治療の新たな可能性～ Invited

    星野歩子

    第31回日本医学会総会2023東京　2023/04/23

  33. Inter-organ communication via exosomes: roles in disease etiology and detection Invited

    2023/04/20

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Industrial Property Rights 5

  1. マイクロウェルアレイ，その製造方法，及び単一細胞由来エクソソームの解析方法

    尾上 弘晃, 山形, 智咲, 板井, 駿, 倉科, 佑太, 星野 歩子

    Property Type: Patent

  2. RADIOLABELLED EXTRACELLULAR VESICLES FOR TREATMENT, IMAGING, AND DETECTION OF TUMORIGENESIS AND/OR METASTATIC PROGRESSION

    David Lyden, Anastasia Nikolopoulou, Shankar Vallabhajosula, Hector Peinado, Ayuko Hoshino, Irina Matei

    Property Type: Patent

  3. EXTRACELLULAR VESICLE NANOCAGE HYBRIDS AND INTEGRIN COUPLING OF NANOCAGES FOR THE TREATMENT OF METASTATIC CANCER

    David Lyden, Ayuko Hoshino, Haiying Zhang, Irina Matei, Serena Lucotti

    Property Type: Patent

  4. EXOSOMAL TUMOR BIOMARKERS AND COLLECTIONS THEREOF

    David Lyden, Ayuko Hoshino, Han Sang Kim, Linda Bojmar

    Property Type: Patent

  5. METHODS AND REAGENTS FOR DETERMINATION AND TREATMENT OF ORGANOTROPIC METASTASIS

    David Lyden, Ayuko Hoshino, Bruno Da Silva

    Property Type: Patent

Research Projects 16

  1. Context‑dependent mechanisms underlying the actions of precursor and mature mitokine GDF15 in peripheral tissues

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tokyo University of Science

    2026/04/01 - 2029/03/31

  2. Maternal circadian rhythm during pregnancy and disease inheritance to next generations through exosomes

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Keio University

    2025/04/01 - 2029/03/31

  3. 胎盤由来エクソソームによる母体臓器への影響とその生理的意義についての包括的理解

    星野 歩子, 佐伯 春美, 林 大久生, 橋本 彩子

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(A)

    Institution: 東京大学

    2025/04/01 - 2028/03/31

  4. 母胎連関エクソソームが司る自閉症発症機序の解明

    星野 歩子

    Offer Organization: 科学技術振興機構

    Category: 戦略的な研究開発の推進/創発的研究支援事業

    2022 - 2028

    More details Close

    発達障害のひとつである自閉症は、生まれつきの脳の機能障害が原因だと考えられているが、その詳細は未だ解明されていません。エクソソームは全ての細胞から産生される微小胞であり、新たな細胞間コミュニケーションツールとして着目されています。本研究は、自閉症の病態についてエクソソームを母胎間媒体とした作業仮説を挙げ、「母体と胎児の間をエクソソームが往来し、胎児の脳発達に影響をもたらす機構」について検証します。

  5. A Comprehensive Amino Acid Transporter-Based Therapeutic Strategy for Lethal Prostate Cancer

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Chiba University

    2024/04/01 - 2027/03/31

  6. A study to predict the prognosis of adolescent onset schizophrenia from the perspective of myelination

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Fujita Health University

    2024/04/01 - 2027/03/31

  7. Development of In-Depth Top-Down Proteomics Method for Comprehensive Analysis of Human Proteoforms

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

    Institution: Ehime University

    2022/10/07 - 2025/03/31

  8. The role of exosome in brain-organ communication

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Transformative Research Areas (A)

    Institution: Tokyo Institute of Technology

    2020/11/19 - 2025/03/31

  9. Glia decoding: deciphering information critical for brain-body interactions

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Transformative Research Areas (A)

    Institution: The University of Tokyo

    2020/11/19 - 2025/03/31

  10. 自閉症児父親由来血漿エクソソームを用いた自閉症予測診断および病態発症機構の解析

    星野 歩子

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 挑戦的研究(萌芽)

    Institution: 東京工業大学

    2021/07/09 - 2023/03/31

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    申請者はこれまで、がんならびに自閉スペクトラム症という異なる病態を呈する疾病のなかで、エクソソームという共通した細胞間コミュニケーションメカニズムを介して、脳へそれぞれのエクソソームが特有の影響を与えることを証明してきた。このエクソソーム研究を自閉スペクトラム症においてより深く理解するため、本研究ではこれまで解析されてきていない父親の血漿由来エクソソームについて知識を深めていく。我々は、一見関連のなさそうな父親の血漿中エクソソームに着目することで自閉スペクトラム症の遺伝的要因・環境的要因に迫るとともに、胎児期の自閉スペクトラム症発症機序について知識を深められると考えており、挑戦的かつ芽生え期研究として適していると理解する。 本年度は自閉スペクトラム症児の父親由来エクソソームと定型発達児の父親由来エクソソームの解析を行い、その含有タンパク質に違いがあることを明らかにした。検出されたタンパク質の種類は共に同程度であり、それぞれの網羅的解析の結果を機械学習を用いて解析をするとそれぞれのグループが綺麗に分かれることがわかった。また、二つのグループを分ける含有量が有意に異なる分子も明らかにすることができた。また、ナノサイトを用いたエクソソームサイズについては二つのグループに差はみられず、1mLの血漿中に存在するエクソソーム数も同程度であった。これらの情報から、二つのグループの相違を明らかにできたので、今後その生物学的意義などについて検討を進める。

  11. Deciphering the heterogeneity of the cancer-derived exosomes and single cell analysis of exosome uptaken cells

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tokyo Institute of Technology

    2020/04/01 - 2023/03/31

  12. 肺転移性がん細胞ダイバーシティーとそのエクソソームの多様性と機能解析

    星野 歩子

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 新学術領域研究(研究領域提案型)

    Category: 新学術領域研究(研究領域提案型)

    Institution: 東京大学

    2020/04/01 - 2022/03/31

    More details Close

    がんの転移形成には原発からの離脱・浸潤、血管への侵入、転移先臓器内血管の崩壊、そして転移先へのがん細胞の生着・増殖という多段階の障壁を乗り越える必要がある。この全てのステップを１細胞および１細胞から産生されたエクソソームがなし得るのではなく、がん組織として多様性を持つ組織集団がそれぞれ別の役割を果たすことで達成していることが考えられる。これは臓器特異性を持つ組織集団であっても同様であり、様々なステップに関わる細胞およびエクソソーム解析は転移抑制を目指す治療に求められている。本研究では、肺への臓器特異的転移能を持つ乳がん細胞をクローニングし、それぞれの細胞の増殖・転移能を計測するとともに、それぞれの細胞が産生するエクソソームがどの様な挙動を示すのか、転移形成へどの様な機能を持っているのかについて調べる。 シングルエクソソーム解析ができるExoViewを用いて肺転移性がん細胞由来エクソソームの多様性について解析を行った。その結果、肺へエクソソームを導く役割をしているインテグリンα６β４は骨転移性がん細胞由来エクソソームに比べて１０倍近く多いものの、肺転移性がん細胞由来エクソソーム全体の中では一握りにとどまることがわかった。 このことから、肺転移性がん細胞の中のどの細胞が特定のエクソソームを産生しているのか、またその細胞はどのような形質をもっているのかを調べるためにクローニングを本年度行い、独立したクローン細胞株を樹立させた。また、それぞれのクローンからエクソソームを回収した。

  13. 脳選択的にターゲットする疾患関連エクソソームの解析

    Offer Organization: 科学技術振興機構(JST)

    System: さきがけ

    2019/04 - 2022/03

  14. Exosome analysis linking maternal immune cells and fetal brain nervous system

    Hoshino Ayuko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Research Activity Start-up

    Institution: Tokyo Institute of Technology

    2019/08/30 - 2021/03/31

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    From this study, we have found that exosomal protein cargo differs between mother who has children with Autism and mother who has neurotypical children. We further elucidated that those exosomes, when injected in pregnant mice, are uptaken by embryo. This data reveals that maternal exosomes are capable of passing through placental barrier and could potentially effect embryonic development. We further determines that specific bone marrow derived cells in maternal body are responsible for the exosomal cargo differences between mother with Autistic child and neurotypical child.

  15. The role of breast cancer exosomes in organotropic metastasis Competitive

    Ayuko Hoshino

    Offer Organization: Susan G. Komen Breast Cancer foundation

    2015/11 - 2018/10

  16. がん間質を構成するヒト血管外膜由来間葉系幹/前駆細胞による腫瘍進展促進機構の解明

    星野 歩子

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 特別研究員奨励費

    Category: 特別研究員奨励費

    Institution: 東京大学

    2009 - 2010

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    ヒト血管外膜由来線維芽細胞(hVAFs)による肺腺がん細胞株(A549)の腫瘍形成上昇機構の解明を行う為に、hVAFsよりもA549細胞の腫瘍形成促進能が低い肺組織由来線維芽細胞(hLFs)とhVAFsの遺伝子発現の網羅的解析を行った。その結果、肺腺がん患者のがん間質で発現が高いと予後不良が報告されているPodoplanin (PDPN)がhVAFsで発現が高いことが分かった。タンパク発現もwestern blot,flow cytometryで検討した結果hVAFsでhLFsより発現が高いことが分かった。FACSを用いてhVAFsにおけるPDPN陽性細胞と陰性細胞を分取し、それぞれをA549細胞とマウス皮下へ移植した結果、PDPN陽性細胞との共移植群で腫瘍形成が促進された。また、PDPN陽性とA549細胞共移植群の腫瘍形成時期はPDPN陰性群との共移植より早いが、腫瘍形成が確認出来てからの腫瘍体積の増加曲線はPDPN陽性共移植群と陰性共移植群で同様であることが分かった。同様の結果がhLFsにおけるPDPN陽性細胞と陰性細胞でも得られた。このことから、PDPN陽性細胞は腫瘍形成促進に寄与することが示唆され、hVAFsとhLFsに含まれるPDPN陽性細胞の量の差が腫瘍形成時期に違いが見られた理由である可能性が考えられた。更にPDPN陽性hVAFsとA549を共移植したマウスでよりリンパ節及び肺への転移が促進されていることが分かった。次に、hVAFsにおけるPDPN発現をshRNAにより抑制し、その時のA549腫瘍形成へ与える影響を調べると、hVAFsによるA549腫瘍形成促進が打ち消されることが確認できた。hVAFsにPDPNを強発現させると(>80%陽性)A549細胞の腫瘍形成率が上昇した。以上より、hVAFsにおけるPDPNは腫瘍形成能上昇に寄与する機能分子であることが分かった。

Show all Show first 5

Social Activities 5

  1. "ST-AR = STudent ‒ Academia Research Project" 高校生が研究者の日常を体験できる 『研究インターンシップ』の機会を増やすことを目的とした団体

    https://st-ar.org/

    2024/08/01 - Present

  2. 内閣府 科学技術振興機構・文部科学省・経済産業省共催「動画公開セミナー理系で広がる私の未来2023」

    理工チャレンジ

    2023/07/07 - Present

  3. 第10回先端研クロストーク「コミュニケーションが創る先端」

    第10回先端研クロストーク

    2024/03/01 - 2024/03/01

  4. 星野研修室 高校生インターン

    2023/08/14 - 2023/08/18

  5. 東京工業大学トップとハーバード大学の先端科学者が語る「理想の研究と教育環境」

    https://www.titech.ac.jp/news/2022/064827

    2022/07/15 -

Media Coverage 5

  1. 「幕女」の独立心、育んだ渋幕

    株式会社 毎日新聞社　毎日新聞　「母校をたずねる」 インタビュー記事

    2024/07/03

    Type: Newspaper, magazine

  2. 一番大切なのは論文発表より治療への貢献

    読売新聞社　科学面［サイエンス Ｈｕｍａｎ］

    2023/05/21

    Type: Newspaper, magazine

  3. Freeing up Japan's PhD potential Myself

    nature　https://www.nature.com/articles/d41586-023-00659-0

    2023/03/08

    Type: Internet

  4. Education in Japan: Two Pioneering Women Empowering New Directions | JAPAN Forward (japan-forward.com)

    JAPAN Forward

    2023/02/10

    Type: Internet

  5. Forbes JAPAN WOMEN AWARD 2022 ジェンダー後進国の「ファーストペンギン」たち

    Forbes JAPAN 2023年1月号　▶︎特集記事② FEATURE STORY 2 Forbes JAPAN WOMEN AWARD 2022 ジェンダー後進国の「ファーストペンギン」たち

    2022/11/25

    Type: Newspaper, magazine

Other 2

  1. 2024InaRISフェロー紹介動画 | 稲盛財団WEBサイト

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    星野 歩子 | 公益財団法人 稲盛財団 https://www.inamori-f.or.jp/recipient/hoshino-ayuko/

  2. General Participant of 6th Japanese-American-German Frontiers of Science (FoS) Symposium supported by JSPS