エクソソームによる疾患機構解明の新しいストーリー

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Outline of Hoshino Laboratory, UTokyo.

Concept

コンセプト
全ての細胞から産生されるエクソソームは、新たな細胞間コミュニケーションツールとして様々な疾患に関わることが示唆されています。ウイルス程の大きさの微小胞であるエクソソームが、臓器特異的な転移や自閉症など、まだ原因や機構が解明されていない疾患を引き起こす影響力を紐解き、将来的には治療につながるパラダイムシフトを起こすことを目指して研究しています。

Publication

研究論文
NEW POST
2024.07.12
  • ・Yamagata C, Hamazaki Y, Nakazato T, Itai S, Honjo M, Kato M, Kurashina Y, Asai M, Hoshino A*, Onoe H*. Oil-sealed RGD-modified alginate hydrogel microwell array for analysis of single-cell-derived extracellular vesicles and particles. Microsyst Nanoeng 11, 238 (2025)
  • ・Terai S, Asonuma M, Hoshino A, Kino-Oka M, Ochiya T, Okada K, Sato Y, Takahashi Y, Tobita M, Tsuchiya A. Guidance on the clinical application of extracellular vesicles. Regenerative Therapy, Mar 7:29:43-50. doi: 10.1016/j.reth.2025.02.008. eCollection (2025)
  • ・Hirosawa K, Sato Y, Kasai R, Yamaguchi E, Komura N, Ando H, Hoshino A, Yokota Y & Suzuki K. Uptake of small extracellular vesicles by recipient cells is facilitated by paracrine adhesion signaling. Nat Commun 16, 2419 (2025)
  • ・Bojmar L, Zambirinis CP, Hernandez J, Chakraborty J,  Shaashua L, Kim J, Johnson KE, Hanna S, Askan G, Burman J, Ravichandran H, Zheng J, Jolissaint JS, Srouji R, Song Y, Choubey A, Kim HS, Cioffi M, Beek EV, Sigel C, Jessurun J, Riestra PV, Blomstrand H, Jönsson C, Jönsson A, Lauritzen P, Buehring W, Ararso Y, Hernandez D, Vinagolu-Baur JP, Friedman M, Glidden C, Firmenich L, Lieberman G, Mejia DL, Nasar N, Mutvei AP, Paul DM, Bram Y, Costa-Silva B, Basturk O, Boudreau N, Zhang H, Matei IR, Hoshino A, Kelsen D, Sagi I, Scherz A, Scherz-Shouval R, Yarden Y, Oren M, Egeblad M, Lewis JS, Keshari K, Grandgenett PM, Hollingsworth MA, Rajasekhar VK, Healey JH, Björnsson B, Simeone DM, Tuveson DA, Iacobuzio-Donahue CA, Bromberg J, Vincent CT, O’Reilly EM, DeMatteo RP, Balachandran VP,D’Angelica MI, Kingham TP, Allen PJ, Simpson AL, Elemento O, Sandström P, Schwartz RE, Jarnagin WR & Lyden D.Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer. nature medicine 2024, Published online: 28 June 2024, doi: 10.1038/s41591-024-03075-7(2024)
  • ・Bojmar L, Kim HS, Sugiura K, Heissel S, Lucotti S, Cioffi M, Johnson KE, Cohen-Gould L, Zhang H, Molina H, Matei IR, Lyden D, Hoshino A*. Protocol for cross-platform characterization of human. STAR Protoc 5(1)102754 (2024)
  • ・Uryu K, Soplop N, P. Sheahan T,  Catanese MT, Huynh C, Pena J, Boudreau N, Matei I, Kenific C, Hashimoto A, Hoshino A, Rice CM, Lyden D. Advancement in Cellular Topographic and Nanoparticle Capture Imaging by High Resolution Microscopy Incorporating a Freeze-Drying and Gaseous Nitrogen-based Approach. bioRxiv 2023 Sep 28:2023.09.28.559906. doi: 10.1101/2023.09.28.559906.(2023)
  • ・Kishimoto T, Agetsuma M, Hoshino A, Takahashi H. Needle-Type Pressure Sensor with Silicone Oil and Parylene Membrane inside for Minimally Invasive Measurement. 電気学会論文誌 E (IEEJ Transactions on Sensors and Micromachines)2023, 143(7)148-155, https://doi.org/10.1541/ieejsmas.143.148(2023)
  • ・Takemori A, Kaulich PT, Konno R, Kawashima Y, Hamazaki Y, Hoshino A, Tholey A, Takemori N. GeLC-FAIMS-MSworkflowforin-depthmiddle-downproteomics. Proteomics 2023, https://doi.org/10.1002/pmic.202200431(2023)
  • ・Suwatthanarak T, Ito K, Tanaka M, Sugiura K, Hoshino A, Miyamoto Y, Miyado K, Okochi M. A peptide binding to the tetraspanin CD9 reduces cancer metastasis. Biomaterials Advances 2023, 146
  • ・Nasiri Kenari A,… , Hoshino A. Serum/Plasma Proteomics: Methods and
    Protocols
    2023, DOI:10.1007/978-1-0716-2978-9_19(2023)
  • ・Khan I, Gril B, Hoshino A, Yang HH, Lee MP, Difilippantonio S, Lyden D & Steeg PS. Metastasis suppressor NME1 in exosomes or liposomes conveys motility and migration inhibition in breast cancer model systems. Clinical & Experimental Metastasis 2022, 39:815–831(2022)
  • ・Hashimoto A, Sugiura K, Hoshino A*. Impact of exosome-mediated feto-maternal interactions on pregnancy maintenance and development of obstetric complications. J Biochem 169(2):163-171 (2021)
  • ・Bojmar L, Sang Kim H, Tobias G, Vatter F, Lucotti S, Ennu Gyan K, Kenific C, Wan Z, Kim KA, Kim D, Hernandez J, Pascual V, Heaton T, La Quaglia M, Kelsen D, Trippett T, Jones D, Jarnagin WR, Matei IR, Zhang H, Hoshino A*, Lyden D*. Extracellular vesicle and particle isolation from human and murine cell lines, tissues, and bodily fluids. STAR Protoc 2(1)100225 (2021)
  • Hoshino A*, Sang Kim H, Bojmar L, Ennu Gyan K, Cioffi M, Hernandez J, Zambirinis CP, Rodrigues G, Molina H, Heissel S, Tesic Mark M, Steiner L, Benito-Martin A, Lucotti S, Di Giannatale A, Offer K, Nakajima M, Williams C, Nogués L, Pelissier Vatter FA, Hashimoto A, Davies AE, Freitas D, Kenific C, Ararso Y, Buehring W, Lauritzen P, Ogitani Y, Sugiura K, Takahashi N, Aleckovic M, Bailey KA, Jolissant JS, Wang H, Harris A, Schaeffer LM, Posner Z, Balachandran VP, Khakoo Y, Raju P, Scherz A, Sagi I, Scherz-Shouval R, Yarden Y, Oren M, Petriccione M, De Braganca K, Donzelli M, Fischer C, Vitolano S, Wright G, Ganshaw L, Marrano M, Ahmed A, DeStefano J, Danzer E, Roehrl MH, Lacayo NJ, Vincent T, Weiser MR, Brady MS, Meyers P, Wexler LH, Ambati S, Chou AJ, Slotkin E, Modak S, Roberts S, Basu E, Diolaiti D, Krantz B, Cardoso F, Simpson AL, Berger M, Rudin CM, Simeone DM, Jain M, Ghajar CM, Batra SK, Stanger BZ, Bui J, Brown KA, Rajasekhar VK, Healey JH, de Sousa M, Kramer K, Sheth S, Baisch J, Pascual V, Heaton TE, La Quaglia MP, Pisapia DJ, Schwartz R, Zhang H, Liu Y, Shukla A, Sarte L, DeClerck Y, LaBarge M, Bissell MJ, Grandgenett P, Hollingsworth M, Bromberg J, Costa-Silva B, Peinado H, Kang Y, Garcia BA, O’Reilly E, Kelsen D, Trippett TM, Jones DR, Matei I, Jarnagin WR, Lyden D. Extracellular Vesicle and Particle biomarkers define multiple human cancers. Cell 182(4):1044-1061 (2020).
  • ・Rodrigues G*, Hoshino A*, Matei IR, Scandariato I, Kenific CM, Kim HS, Casanova-Salas I, Dai D, Badwe CR, Gril B, Mark MT, Dill BD, Molina H, Benito-Martin A, Bojmar L, Offer K, LaPlant Q, Ararso Y, Buehring W, Wang H, Juan X, Liu Y, Sabari JK, Shin SJ, Narula N, Rajasekhar VK, Zhang H, Costa-Silva B, Rafii S, Rudin CM, Jones DR, Steeg PS, Peinado H, Ghajar CM, Bromberg J, Pisapia D, de Sousa M, Lyden D. Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis. Nat Cell Biol 527(7578):329-35 (2019)
  • ・Prakash V, Carson BB, Feenstra JM, Dass RA, Sekyrova P, Hoshino A, Petersen J, Guo Y, Parks MM, Kurylo CM, Batchelder JE, Haller K, Hashimoto A, Rundqivst H, Condeelis JS, Allis CD, Drygin D, Nieto MA, Andang M, Percipalle P, Bergh J, Adameyko I, Farrants AO, Hartman J, Lyden D, Pietras K, Blanchard SC, Vincent CT. Ribosome biogenesis during cell cycle arrest fuels EMT in development and disease. Nature Communications 2019 May 8;(1):2110(2019)
  • ・Wittkowski KM, Dadurian C, Seybond MP, Kim HS, Hoshino A, Lyden D. Complex polymorphisms in endocytosis genes suggest alpha-cyclodextrin as a treatment for breast cancer. PLoS One 2018 Jul 2;13(7):e0199012(2018)
  • ・Zhang H, Freitas D, Kim HS, Fabijanic K, Li Z, Chen H, Mark MT, Molina H, Martin AB, Bojmar L, Fang J, Rampersaud S, Hoshino A, Matei I, Kenific C, Nakajima M, Mutvei AP, Sansone P, Buehring W, Wang H, Jimenez JP, Cohen-Gould L, Paknejad N, Brendel M, Manova-Todorova K, Magalhaes A, Ferreira JA, Osorio H, Silva AM, Massay A, Cubillos-Ruiz JR, Galletti G, Giannakakou P, Cuervo AM, Blenis J, Schwartz R, Brady MS, Peinado H, Bromberg J, Matsui H, Reis CA, Lyden D. Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric-flow field-flow fractionation. Nat Cell Biol 20(3):332-343 (2018)
  • ・Sansone P, Savini C, Kurelac I, Chang Q, Amato LB, Strillacci A, Stepanova A, Lommarini L, Mastroleo C, Daly L, Galkin A, Thakur BK, Soplop N, Uryu K, Hoshino A, Norton L, Bonafe M, Cricca M, Gasparre G, Lyden D, Bromberg J. Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer. The Proceedings of the National Academy of Sciences USA 2017 Oct 24; 111(43):E9066-E9075(2017)
  • Hoshino A, Lyden D. Metastasis: Lymphatic detours for cancer. Nature 2017 Jun 28;546(7660):609-610(2017)
  • ・Peinado H, Zhang H, Matei IR, Costa-Silva B, Hoshino A, Rodrigues G, Psaila B, Kaplan RN, Bromberg JF, Kang Y, Bissell MJ, Cox TR, Giaccia AJ, Erler JT, Hiratsuka S, Ghajar CM, Lyden D. Pre-metastatic niches: organ-specific homes for metastases. Nature Reviews Cancer 2017 May;17(5):302-317(2017)
  • ・Rampersaud S, Fang J, Wei Z, Fabijanic K, Silver S, Jaikaran T, Ruiz Y, Houssou M, Yin Z, Zheng S, Hashimoto A, Hoshino A, Lyden D, Mahajan S, Matsui H. The effect of cage shape on nanoparticle-based drug carriers: Anti-cancer drug release and efficacy via receptor blockade using dextran-coated iron oxide nanocages. Nano Letters 2016 Dec 14;16(12):7357-7363(2016)
  • Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, Molina H, Kohsaka S, Di Giannatale A, Ceder S, Singh S, Williams C, Soplop N, Uryu K, Pharmer L, King T, Bojmar L, Davies AE, Ararso Y, Zhang T, Zhang H, Hernandez J, Weiss JM, Dumont-Cole VD, Kramer K, Wexler LH, Narendran A, Schwartz GK, Healey JH, Sandstrom P, Jorgen Labori K, Kure EH, Grandgenett PM, Hollingsworth MA, de Sousa M, Kaur S, Jain M, Mallya K, Batra SK, Jarnagin WR, Brady MS, Fodstad O, Muller V, Pantel K, Minn AJ, Bissell MJ, Garcia BA, Kang Y, Rajasekhar VK, Ghajar CM, Matei I, Peinado H, Bromberg J, Lyden D. Tumour exosome integrins determine organotropic metastasis. Nature 527, 329-335 (2015)
  • ・Costa-Silva B, Aiello NM, Ocean AJ, Singh S, Zhang H, Thakur BK, Becker A, Hoshino A, Mark MT, Molina H, Xiang J, Zhang T, Theilen TM, Garcia-Santos G, Williams C, Ararso Y, Huang Y, Rodrigues G, Shen TL, Labori KJ, Lothe IM, Kure EH, Hernandez J, Doussot A, Ebbesen SH, Grandgenett PM, Hollingsworth MA, Jain M, Mallya K, Batra SK, Jarnagin WR, Schwartz RE, Matei I, Peinado H, Stanger BZ, Bromberg J, Lyden D. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol 17(6):816-26 (2015)
  • ・Thakur BK, Zhang H, Becker A, Matei I, Huang Y, Costa-Silva B, Zheng Y, Hoshino A, Brazier H, Xiang J, Williams C, Rodriguez-Barrueco R, Silva JM, Zhang W, Hearn S, Elemento O, Paknejad N, Manova-Todorova K, Welte K, Bromberg J, Peinado H, Lyden D. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Research 2014 Jun;24(6):766-9(2014)
  • ・Ishii G, Hashimoto H, Atsumi N, Hoshino A, Ochiai A. Morphophenotype of floating colonies derived from a single cancer cell has a critical impact on tumor-forming activity. Pathology International 2013 Jan;63(1):29-36(2013)
  • ・Peinado H, Ale?kovi? M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, Hergueta-Redondo M, Williams C, Garcia-Santos G, Ghajar CM, Nitadori-Hoshino A, Hoffman C, Badal K, Garcia BA, Callahan MK, Yuan J, Martins VR, Skog J, Kaplan RN, Brady MS, Wolchok JD, Chapman PB, Kang Y, Bromberg J, Lyden D. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nature Medicine 2012 Jun;18(6):883-91(2012)
  • ・Ito S, Ishii G, Hoshino A, Hashimoto H, Neri S, Kuwata T, Higashi M, Nagai K, Ochiai A. Tumor promoting effect of podoplanin-positive fibroblasts is mediated by enhanced RhoA activity. Biochemical and Biophysical Research Communications 2012 May25; 422(1):194-9 (2012)
  • Hoshino A, Ishii G, Ito T, Aoyagi K, Ohtaki Y, Nagai K, Sasaki H, and Ochiai A. Podoplanin-positive fibroblasts enhance lung adenocarcinoma tumor formation. Cancer Res 71(14):4769-79 (2011)
  • ・Ishii G, Hashimoto H, Asada K, Ito T, Hoshino A, Fujii S, Kojima M, Kuwata T, Harigaya K, Nagai K, Ushijima T, and Ochiai A. Fibroblasts associated with cancer cells keep enhanced migration activity after separation from cancer cells: a novel character of tumor educated fibroblasts. International Journal of Oncology 2010 Aug;37(2):317-25 (2010)
  • ・Ito TK, Ishii G, Saito S, Yano K, Hoshino A, Suzuki T, and Ochiai A. Degradation of soluble VEGF receptor-1 by MMP-7 allows VEGF access to endothelial cells. Blood 2009 Mar 5;113(10):2363-9 (2009)
  • Hoshino A, Chiba H, Nagai K, Ishii G, and Ochiai A. Human vascular adventitial fibroblasts contain mesenchymal stem/progenitor cells. Biochem Biophys Res Commun 368(2):305-10 (2008)

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