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Inhibition mechanism of peritoneal dissemination of cancer-derived exosomes by innate immune system

Research Project

Project/Area Number 18K15315
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionShiga University of Medical Science

Principal Investigator

Tokuda Aya  滋賀医科大学, 医学部, 特任助教 (80814392)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords自然免疫 / 大腸癌 / エクソソーム / NK細胞 / ヌードマウス
Outline of Final Research Achievements

We collected exosomes from CT26 cells, a mouse-derived colon cancer cell line, and investigated the effect of exosomes on macrophages. When mouse-derived spleen cells were stimulated with CT26-derived exosomes, the production of IFNgamma was increased, suggesting that CT26-derived exosomes activate NK cells. Cytokine array showed an increase in chemokines and IFN-gamma in response to cancer-derived exosome. Stimulation of mouse intraperitoneal cells with cancer-derived exosomes increased the mRNA level of iNOS, suggesting that exosomes promote the differentiation of intraperitoneal macrophages into M1.

Academic Significance and Societal Importance of the Research Achievements

エクソソームは、癌の増殖や転移に関わるとされ、癌細胞由来のエクソソームが特定の臓器に取り込まれることで転移前ニッチェの形成に関わるとの報告がある。しかし、これらのエクソソームが 癌進展における自然免疫への役割については未だ明らかではない。今回、大腸がんモデルマウスのCT26大腸がん由来のエクソソームを腹腔内投与することで、NK細胞によるIFNγの産生が促進された。これらのエクソソームによる免疫の活性化は機序は、まだ明らかではないが、今後、他の癌種の腹膜転移を抑制する新しい戦略を設計する上で有益であると考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2021 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (2 results)

  • [Journal Article] Cancer-derived Exosomes Activate Immune Surveillance and Suppress Peritoneal Metastasis of Murine Colonic Cancer2021

    • Author(s)
      TOKUDA AYA、MIYAKE TORU、YASUKAWA DAIKI、IKUTA DAIJI、MUKAISHO KEN-ICHI、MURATA SATOSHI、SHIMIZU TOMOHARU、TANI MASAJI
    • Journal Title

      Anticancer Research

      Volume: 41 Issue: 3 Pages: 1327-1339

    • DOI

      10.21873/anticanres.14890

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] 大腸癌由来エクソソームはM1マクロファージの誘導により腹膜播種を抑制する2019

    • Author(s)
      徳田 彩
    • Organizer
      バイオセラピィ学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Exosomes derived from murine colon cancer cell line inhibit peritoneal dissemination in vivo.2018

    • Author(s)
      Aya Tokuda, Toru Miyake, Daiji Ikuta, Satoshi Murata, Ken-ichi Mukaisho and Masaji Tani
    • Organizer
      日本癌学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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