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Colorectal cancer-derived extracellular vesicles induce tumor immunotolerance

Research Project

Project/Area Number 26870243
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Immunology
Tumor biology
Research InstitutionGifu University

Principal Investigator

Yamada Nami  岐阜大学, 大学院医学系研究科, 助教 (40727319)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords細胞外小胞 / エクソソーム / 細胞間コミュニケーション / がん微小環境 / Extracellular vesicles / 免疫寛容 / 膜小胞 / 免疫抑制 / エクソゾーム / 癌微小環境における細胞間コミュニケーション
Outline of Final Research Achievements

Emerging studies on tumor cell-derived extracellular vesicles (EVs) have shown the biological significance in tumor development and microenvironment through reprogramming immune cells around cancer cells. In this study, we used colorectal cancer cells as EV-donor, and T cells as EV-recipient to examine whether EVs impair the T cell function.
As a result, we found that colorectal cancer cell-derived EVs (CRC-EVs) were enriched with TGF-β1. Interestingly, CRC-EVs induced phenotypic alteration of the T cells to Treg-like cells through activating TGF-β/Smad signaling and inactivating SAPK signaling. Furthermore, the CRC-EVs-induced-Treg-like cells had a remarkable tumor-growth promoting activity in vitro and in vivo. These results suggest that colorectal cancer cells utilize EVs to tame immune cells for their prosperity.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (9 results)

All 2017 2016 2014

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Acknowledgement Compliant: 6 results,  Open Access: 4 results) Presentation (3 results)

  • [Journal Article] Extracellular vesicles: Emerging mediators of intercellular communication and tumor angiogenesis2017

    • Author(s)
      Yamada NO
    • Journal Title

      Annals of Translational Medicine

      Volume: 5 Issue: 3 Pages: 59-59

    • DOI

      10.21037/atm.2017.01.14

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Extracellular vesicles in cancer2016

    • Author(s)
      Yamada N, Akao Y
    • Journal Title

      Advances in biomembranes and lipid self-assembly

      Volume: 23 Pages: 187-204

    • DOI

      10.1016/bs.abl.2016.01.004

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Extracellular vesicles in cancer: current status and challenges2016

    • Author(s)
      Yamada NO
    • Journal Title

      Translational Cancer Research

      Volume: 5 Issue: S3 Pages: S561-S563

    • DOI

      10.21037/tcr.2016.09.14

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A Novel Role of Dickkopf-Related Protein 3 in Macropinocytosis in Human Bladder Cancer T24 Cells2016

    • Author(s)
      Tsujimura N, Yamada NO, Kuranaga Y, Kumazaki M, Shinohara H, Taniguchi K, Akao Y
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 17 Issue: 11 Pages: 1846-1846

    • DOI

      10.3390/ijms17111846

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Colorectal cancer cell-derived extracellular vesicles induce phenotypic alteration of T cells into tumor-growth supporting cells with transforming growth factor-β1-mediated suppression2016

    • Author(s)
      Yamada N., Kuranaga Y., Kumazaki M., Shinohara H., Taniguchi K., Akao Y.
    • Journal Title

      Oncotarget

      Volume: 不明 Issue: 19 Pages: 27033-43

    • DOI

      10.18632/oncotarget.7041

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Colorectal cancer cell-derived microvesicles containing microRNA-1246 promote angiogenesis by activating Smad 1/5/8 signaling elicited by PML down-regulation in endothelial cells2014

    • Author(s)
      Yamada, N. Tsujimura, N. Kumazaki, M. Shinohara, H. Taniguchi, K. Nakagawa, Y. Naoe, T. Akao, Y.
    • Journal Title

      Biochim Biophys Acta

      Volume: 1839 Issue: 11 Pages: 1256-1272

    • DOI

      10.1016/j.bbagrm.2014.09.002

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Colorectal cancer-derived extracellular vesicles induce tumor immunotolerance2017

    • Author(s)
      Nami O. Yamada, Yuki Kuranaga, Shuji Matsuda, Yukihiro Akao, Takao Senda
    • Organizer
      第122回日本解剖学会総会・学術集会
    • Place of Presentation
      長崎大学坂本キャンパス
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] 大腸がんにおける細胞外小胞と免疫寛容誘導メカニズム2016

    • Author(s)
      山田名美、倉永祐希、松田修二、赤尾幸博、千田隆夫
    • Organizer
      第76回日本解剖学会中部支部学術集会
    • Place of Presentation
      信州大学医学部附属病院 大会議室
    • Year and Date
      2016-10-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] 大腸癌分泌膜小胞による免疫寛容誘導メカニズム2014

    • Author(s)
      山田名美、倉永祐希、赤尾幸博
    • Organizer
      第18回日本がん免疫学会総会
    • Place of Presentation
      愛媛県松山市
    • Year and Date
      2014-07-30 – 2014-08-01
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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