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  • Hoshino, AyukoWeill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA (author)

Tumour exosome integrins determine organotropic metastasis

  • Article/chapterEnglish2015

Publisher, publication year, extent ...

  • 2015-10-28
  • NATURE PUBLISHING GROUP,2015
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-125329
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-125329URI
  • https://doi.org/10.1038/nature15756DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:132872074URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding Agencies|MSK Cancer Center Support Grant/Core Grant [P30 CA008748]; National Cancer Institute [U01-CA169538]; National Institutes of Health [R01-CA169416]; United States Department of Defense [W81XWH-13-10249, W81XWH-13-1-0425]; Melanoma Research Alliance; Sohn Conference Foundation; Childrens Cancer and Blood Foundation; Manning Foundation; Hartwell Foundation; Fundacao para a Ciencia e a Tecnologia; Nancy C. and Daniel P. Paduano Foundation; Feldstein Foundation; Starr Cancer Consortium; Mary Kay Foundation; Pediatric Oncology Experimental Therapeutic Investigator Consortium (POETIC); James Paduano Foundation; Beth Tortolani Foundation; Malcolm Hewitt Weiner Foundation; Theodore A. Rapp Foundation; American Hellenic Educational Progressive Association 5th District Cancer Research Foundation; Charles and Marjorie Holloway Foundation; Sussman Family Fund; Lerner Foundation; Breast Cancer Alliance; Manhasset Womens Coalition Against Breast Cancer; Ministry of Science and Technology Taiwan [101-2918-I-002-016]; JSPS Postdoctoral Fellowships; Susan G. Komen Postdoctoral Fellowship
  • Ever since Stephen Pagets 1889 hypothesis, metastatic organotropism has remained one of cancers 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 alpha(6)beta(4) and alpha(6)beta(1) were associated with lung metastasis, while exosomal integrin alpha(v)beta(5) was linked to liver metastasis. Targeting the integrins alpha(6)beta(4) and alpha(v)beta(5) 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.

Subject headings and genre

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  • Costa-Silva, BrunoWeill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA (author)
  • Shen, Tang-LongWeill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; National Taiwan University, Taiwan; National Taiwan University, Taiwan (author)
  • Rodrigues, GoncaloWeill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; University of Porto, Portugal (author)
  • Hashimoto, AyakoWeill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; University of Tokyo, Japan (author)
  • Tesic Mark, MilicaRockefeller University, NY 10065 USA (author)
  • Molina, HenrikRockefeller University, NY 10065 USA (author)
  • Kohsaka, ShinjiMem Sloan Kettering Cancer Centre, NY 10065 USA (author)
  • Di Giannatale, AngelaWeill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA (author)
  • Ceder, SophiaKarolinska Institutet (author)
  • Singh, SwarnimaWeill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA (author)
  • Williams, CaitlinWeill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA (author)
  • Soplop, NadineRockefeller University, NY 10065 USA (author)
  • Uryu, KunihiroRockefeller University, NY 10065 USA (author)
  • Pharmer, LindsayMem Sloan Kettering Cancer Centre, NY 10065 USA (author)
  • King, TariMem Sloan Kettering Cancer Centre, NY 10065 USA (author)
  • Bojmar, LindaLinköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA(Swepub:liu)linbo68 (author)
  • Davies, Alexander E.University of Calif Berkeley, CA 94720 USA (author)
  • Ararso, YonathanWeill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA (author)
  • Zhang, TuoWeill Cornell Med, NY 10021 USA (author)
  • Zhang, HaiyingWeill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA (author)
  • Hernandez, JonathanWeill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Mem Sloan Kettering Cancer Centre, NY 10065 USA (author)
  • Weiss, Joshua M.Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA (author)
  • Dumont-Cole, Vanessa D.Mem Sloan Kettering Cancer Centre, NY 10065 USA (author)
  • Kramer, KimberlyMem Sloan Kettering Cancer Centre, NY 10065 USA (author)
  • Wexler, Leonard H.Mem Sloan Kettering Cancer Centre, NY 10065 USA (author)
  • Narendran, AruAlberta Childrens Prov Gen Hospital, Canada (author)
  • Schwartz, Gary K.Columbia University, NY 10032 USA (author)
  • Healey, John H.Mem Sloan Kettering Cancer Centre, NY 10065 USA (author)
  • Sandström, PerLinköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,Region Östergötland, Kirurgiska kliniken US(Swepub:liu)persa07 (author)
  • Jorgen Labori, KnutOslo University Hospital, Norway (author)
  • Kure, Elin H.Oslo University Hospital, Norway (author)
  • Grandgenett, Paul M.University of Nebraska Medical Centre, NE 68198 USA (author)
  • Hollingsworth, Michael A.University of Nebraska Medical Centre, NE 68198 USA (author)
  • de Sousa, MariaWeill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; University of Porto, Portugal (author)
  • Kaur, SukhwinderUniversity of Nebraska Medical Centre, NE 68198 USA (author)
  • Jain, ManeeshUniversity of Nebraska Medical Centre, NE 68198 USA (author)
  • Mallya, KavitaUniversity of Nebraska Medical Centre, NE 68198 USA (author)
  • Batra, Surinder K.University of Nebraska Medical Centre, NE 68198 USA (author)
  • Jarnagin, William R.Mem Sloan Kettering Cancer Centre, NY 10065 USA (author)
  • Brady, Mary S.Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Mem Sloan Kettering Cancer Centre, NY 10065 USA (author)
  • Fodstad, OysteinOslo University Hospital, Norway; University of Oslo, Norway (author)
  • Muller, VolkmarUniversity of Medical Centre, Germany (author)
  • Pantel, KlausUniversity of Medical Centre Hamburg Eppendorf, Germany (author)
  • Minn, Andy J.University of Penn, PA 19104 USA (author)
  • Bissell, Mina J.University of Calif Berkeley, CA 94720 USA (author)
  • Garcia, Benjamin A.University of Penn, PA 19104 USA (author)
  • Kang, YibinPrinceton University, NJ 08544 USA; Rutgers Cancer Institute New Jersey, NJ 08903 USA (author)
  • Rajasekhar, Vinagolu K.Mem Sloan Kettering Cancer Centre, NY 10065 USA (author)
  • Ghajar, Cyrus M.Fred Hutchinson Cancer Research Centre, WA 98109 USA (author)
  • Matei, IrinaWeill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA (author)
  • Peinado, HectorWeill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Spanish National Cancer Research Centre CNIO, Spain (author)
  • Bromberg, JacquelineMem Sloan Kettering Cancer Centre, NY 10065 USA; Weill Cornell Med, NY 10021 USA (author)
  • Lyden, DavidWeill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Mem Sloan Kettering Cancer Centre, NY 10065 USA (author)
  • Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USAWeill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; National Taiwan University, Taiwan; National Taiwan University, Taiwan (creator_code:org_t)

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  • In:Nature: NATURE PUBLISHING GROUP527:7578, s. 329-+0028-08361476-4687

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