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The role of damage-associated molecules in organ-specific metastatic niche

Research Project

Project/Area Number 22K15522
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionThe University of Tokyo

Principal Investigator

Shotaro Eto  東京大学, 先端科学技術研究センター, 特任研究員 (50940087)

Project Period (FY) 2022-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2023: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsがん微小環境 / 転移ニッチ / 腫瘍微小環境
Outline of Research at the Start

がん細胞の転移を支える微小環境(転移ニッチ)は有望な治療標的となりうる。近年の解析から、転移ニッチは原発腫瘍における微小環境とは細胞集団や遺伝子発現が大きく異なる一方で、転移臓器ごとに共通した特徴を示すことがわかってきた。しかし、その差異を生むメカニズムは明らかになっていない。本研究では、死滅したがん細胞から放出される自己由来分子群(DAMPs)に着目し、DAMPsを起点とした組織特異的な転移ニッチ形成メカニズムと肺および肝臓のそれぞれで特異的に働く新規DAMPs分子の同定を目指す。これによって、がんの種類に依らない、転移が存在する解剖学的な”位置”に特異的な新規治療法の提案を目指す。

Outline of Final Research Achievements

In this study, gene expression analysis of metastatic tumour cells and metastatic niche cells was performed to investigate tissue-specific metastatic niche formation mechanisms.
YAP/TAZ signalling was activated in lung metastatic cancer cells compared to the liver metastatic tumour cells. Inhibition of YAP/TAZ delayed tumour growth in the lung and increased peri-tumour CD8+ T cells.
Myeloid cells in liver metastases expressed high levels of Arg1. This phenomenon was also found to be synergistically induced by tumour cell-derived humoral factors and the hypoxic environment of the liver. Gene expression analysis of liver parenchymal cells around tumour cells also showed that a liver parenchymal regenerative response may be occurring around tumour cells.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、臓器特異的な遺伝子発現やシグナル経路を同定することができた。これらを阻害する薬剤は、肺転移および肝転移特異的な治療法になりうる。がんの種類に依らない、転移が存在する解剖学的な”位置”に特異的な新規治療法開発のための足がかりとなる結果を得ることができたと考えている。またがん細胞周囲の肝実質細胞についてはほとんど研究がなされておらず、今後これらの活性化の意義を明らかにすることで、肝転移に特異的な治療法の開発につながると考えられる。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (3 results)

All 2024 2023 2022

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

  • [Journal Article] Potential of HMGB-inhibitory oligodeoxynucleotide ISM ODN to neutrophil recruitment in mouse model of hepatitis2022

    • Author(s)
      Inoue Asuka、Chiba Shiho、Eto Shotaro、Taniguchi Tadatsugu、Yanai Hideyuki
    • Journal Title

      Genes to Cells

      Volume: 28 Issue: 3 Pages: 202-210

    • DOI

      10.1111/gtc.13002

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Exploring the anti-tumour mechanisms of cyclooxygenase (COX) inhibitors through tumour immune microenvironment reprogramming in canine urothelial carcinoma2024

    • Author(s)
      Shotaro Eto, Daiki Kato, Kohei Saeki, Satoshi Kamoto, Ryohei Yoshitake, Masahiro Shinada, Takaaki Iguchi, Shiyu Qin, Masaya Tsuboi, James Chambers, Kazuyuki Uchida, Ryohei Nishimura, Takayuki Nakagawa
    • Organizer
      World Veterinary Cancer Congress 2024
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Book] 実験医学2023年12月号 【炎症老化 Inflammaging】細胞障害関連分子(DAMPs)と炎症老化2023

    • Author(s)
      衞藤翔太郎,柳井秀元
    • Total Pages
      131
    • Publisher
      羊土社
    • ISBN
      9784758125741
    • Related Report
      2023 Annual Research Report

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Published: 2022-04-19   Modified: 2025-01-30  

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