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Analysis of cell-to-cell communication to identify novel targets of radiotherapy

Research Project

Project/Area Number 19K08140
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionKyoto University (2020-2021)
Hokkaido University (2019)

Principal Investigator

Nam Jin-Min  京都大学, 生命科学研究科, 准教授 (60414132)

Co-Investigator(Kenkyū-buntansha) 小野寺 康仁  北海道大学, 医学研究院, 准教授 (90435561)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords放射線 / 小胞輸送 / パラクライン / 細胞間コミュニケーション / エクソソーム / がん細胞
Outline of Research at the Start

放射線療法はがん治療に広く用いられているが、治療効果のさらなる向上には、放射線による細胞への影響の生命科学的な理解が不可欠である。私たちはこれまでに、放射線照射後のがん細胞の生存や浸潤性亢進に関わる分子メカニズムの一端を明らかにしてきた。さらに近年、がん細胞の放射線感受性と、細胞内小胞の分布の変化が密接に関連することを発見した。これらの成果をもとに、放射線照射後にがん細胞から分泌されるエクソソームの役割とその分子メカニズムに現在着目している。本研究は、放射線が照射された細胞の周辺または遠隔細胞への影響に、エクソソームがどのように関連しているか、という問いから展開される。

Outline of Final Research Achievements

Radiation therapy is widely used in cancer treatment, but understanding of the radiation effect on cancer cells is essential to improve therapeutic efficacy. To elucidate the molecular mechanisms of radiotherapy resistance mediated by these pathways, we analyzed vesicular trafficking pathways that specifically regulate factors such as extracellular vesicles secreted from cancer cells after irradiation. In this study, our data suggested that the secreted epiregulin into the extracellular space via Rab27b pathway is involved in radiotherapy resistance of glioblastoma cells.

Academic Significance and Societal Importance of the Research Achievements

がん治療に広く用いられている放射線療法において、治療効果の向上のため、放射線に対するがん細胞の治療抵抗性の理解が必要不可欠である。本研究では、放射線照射後に分泌が促進される因子とその過程を制御する分子が放射線治療抵抗性に関与していることを見出した。本研究成果に基づき、新たに見つかった経路と分泌因子が放射線治療後の腫瘍の増殖を抑え、がん治療効果を向上させるための新規治療標的薬開発に繋がることが期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (12 results)

All 2021 2020 Other

All Int'l Joint Research (3 results) Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (4 results) (of which Invited: 2 results)

  • [Int'l Joint Research] Stanford University(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Stanford University(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Stanford University(米国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] An Overview of the Recent Development of Anticancer Agents Targeting the HIF-1 Transcription Factor2021

    • Author(s)
      Shirai Y, Chow CCT, Kambe G, Suwa T, Kobayashi M, Takahashi I, Harada H, Nam JM.
    • Journal Title

      Cancers

      Volume: 13 Issue: 11 Pages: 2813-2813

    • DOI

      10.3390/cancers13112813

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tumor microenvironment and radioresistance.2021

    • Author(s)
      Suwa T, Kobayashi M, Nam JM, Harada H.
    • Journal Title

      Exp Mol Med.

      Volume: 53 Issue: 6 Pages: 1029-1029

    • DOI

      10.1038/s12276-021-00640-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SPINK1 as a plasma marker for tumor hypoxia and a therapeutic target for radiosensitization.2021

    • Author(s)
      Suwa T, Kobayashi M, Shirai Y, Nam JM, Tabuchi Y, Takeda N, Akamatsu S, Ogawa O, Mizowaki T, Hammond EM, Harada H.
    • Journal Title

      JCI Insight.

      Volume: 6 Issue: 21

    • DOI

      10.1172/jci.insight.148135

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lysosomal trafficking mediated by Arl8b and BORC promotes invasion of cancer cells that survive radiation.2020

    • Author(s)
      Wu PH, Onodera Y, Giaccia AJ, Le QT, Shimizu S, Shirato H, Nam JM.
    • Journal Title

      Communications Biology

      Volume: 27 Issue: 1 Pages: 1-15

    • DOI

      10.1038/s42003-020-01339-9

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rab27b contributes to radioresistance and exerts a paracrine effect via epiregulin in glioblastoma.2020

    • Author(s)
      Nishioka S, Wu PH, Yakabe T, Giaccia AJ, Le QT, Aoyama H, Shimizu S, Shirato H, Onodera Y, Nam JM.
    • Journal Title

      Neuro-Oncology Advances

      Volume: 8 Issue: 1 Pages: 1-13

    • DOI

      10.1093/noajnl/vdaa091

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Rab27bは神経膠芽腫の放射線抵抗性や、Epiregulinを介したパラクライン効果を促進する2021

    • Author(s)
      西岡蒼一郎、呉秉修、矢ヶ部俊彰、Giaccia Amato, Le Qyunh-Thu、小野寺康仁、清水伸一、白土博樹、南ジンミン
    • Organizer
      日本放射線影響学会第64回大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] がん細胞の放射線治療耐性に関わる細胞内小胞輸送のメカニズム2021

    • Author(s)
      Nam Jin-Min
    • Organizer
      第49回放射線による制癌シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 神経膠芽腫の放射線治療効果向上を目指した小胞輸送のメカニズム解析2021

    • Author(s)
      Nam Jin-Min
    • Organizer
      第59回日本癌治療学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Rab27bは神経膠芽腫の放射線抵抗性やパラクライン効果を促進する2020

    • Author(s)
      西岡蒼一郎、呉秉修、矢ヶ部俊彰、Giaccia Amato, Le Qyunh-Thu、小野寺康仁、清水伸一、白土博樹、南ジンミン
    • Organizer
      日本放射線腫瘍学会第32回学術大会
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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