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Elucidation and therapeutic application of a novel metastasis-suppressing niche independent of anti-tumor immunity and NK cells

Research Project

Project/Area Number 20K07592
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionKyushu University

Principal Investigator

Yumimoto Kanae  九州大学, 生体防御医学研究所, 助教 (30596838)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsがん転移 / がん転移ニッチ / cancer niche
Outline of Research at the Start

本申請課題では、single cell RNA-seqを用いて、申請者らが発見した“転移抑制ニッチ”の全体像を探る。具体的には、EGFPを発現した骨髄細胞を移植したマウスと、がん細胞を取り囲む細胞をラベル出来るシステムを用いて、経時的にがんニッチ細胞を回収してsingle cell RNA-seq解析をおこない、転移抑制ニッチに特異的な細胞群を決定する。併せて、どのようなシグナルが転移抑制ニッチを形成するかを見出す。さらに、原発がん非存在下でも“転移抑制ニッチ”を誘導する治療法の開発により、がん転移の予防につなげたいと考えている。

Outline of Final Research Achievements

We found that, a cancer metastasis-suppressing niche is formed at the metastatic site in mice pre-implanted with cancer cells, in contrast to the well-known cancer metastasis-promoting niche. These phenomena were commonly detected in all three types of transplanted cancer cells (B16F10, LLC, and E0771). Based on FACS and single RNA seq analyses of cancer niche cells, we found groups of cells that accumulated in the metastasis suppression niche and groups of cells that decreased in the niche. In addition, ELISA analysis of lung and peripheral blood revealed liquid factors that increase or decrease in a cancer cell transplantation-dependent manner.

Academic Significance and Societal Importance of the Research Achievements

がん患者の死因の大半は転移であり、転移を抑制できればがん患者の予後改善につながる我々の発見はがんの存在により転移が抑制されるというものだが、手術後等、がんの非存在下でも転移抑制環境を構築できれば、予後改善につながることが期待できる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (9 results)

All 2023 2022 2021 2020

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Molecular evolution of Keap1 was essential for adaptation of vertebrates to terrestrial life2023

    • Author(s)
      Kanae Yumimoto, Shigeaki Sugiyama, Saori Motomura, Daisuke Takahashi, Keiichi I. Nakayama
    • Journal Title

      Science Advances

      Volume: in press

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recent insight into the role of FBXW7 as a tumor suppressor2020

    • Author(s)
      Yumimoto Kanae、Nakayama Keiichi I.
    • Journal Title

      Seminars in Cancer Biology

      Volume: 未定 Pages: 1-15

    • DOI

      10.1016/j.semcancer.2020.02.017

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] F-Box Proteins and Cancer2020

    • Author(s)
      Yumimoto Kanae、Yamauchi Yuhei、Nakayama Keiichi I.
    • Journal Title

      Cancers

      Volume: 12 Issue: 5 Pages: 1249-1249

    • DOI

      10.3390/cancers12051249

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Molecular evolution of Keap1 was essential for adaptation of vertebrates to terrestrial life2022

    • Author(s)
      Yumimoto K., Sugiyama S., Takahashi D., Nakayama K.I.
    • Organizer
      The 31st Hot Spring Harbor International Symposium
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Keap1の分子進化は生命の陸上生活への適応に必須である2022

    • Author(s)
      弓本佳苗、高橋大輔、中山敬一
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Fbxw7に非依存的な新規c-MYC分解機構の発見2022

    • Author(s)
      本村早麗、弓本佳苗、中山敬一
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 原発腫瘍が転移巣の微小環境に及ぼす抑制的作用の解析2022

    • Author(s)
      杉山成明、弓本佳苗、久保田晋平、高橋恵生、宮園浩平、中山敬一
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 原発腫瘍によって誘導される転移抑制的な微小環境の解析2021

    • Author(s)
      杉山成明、弓本佳苗、久保田晋平、高橋恵生、宮園浩平、中山敬一
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] Keap1のユビキチン化活性の「減弱」は動物の陸上進出に必要な分子進化である2021

    • Author(s)
      弓本佳苗、高橋大輔、中山敬一
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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