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Visualization and Identification of Mechanisms Regulating the Elimination of Metastatic Lung Cancer Cells in the Brain

Research Project

Project/Area Number 21K16140
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionNagoya University

Principal Investigator

TSUJI TAKAHIRO  名古屋大学, 医学系研究科, 学振特別研究員(PD) (50850046)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords転移性脳腫瘍 / ミクログリア / 微小環境 / 腫瘍免疫 / Don't eat meシグナル / 生体イメージング / 治療開発 / 転移性脳腫瘍モデル
Outline of Research at the Start

これまで申請者は、肺癌(転移性脳腫瘍)と脳内自然免疫細胞を2光子顕微鏡を用いて生体内で可視化し、肺癌細胞が脳内免疫系を活性化することを明らかにした。一方で背景にある免疫―癌細胞間相互作用や分子機構は不明のままである。そこで、本研究は生体で可視化免疫応答を担う分子基盤同定する系を構築することを目的とする。また、体循環系免疫細胞と血管を時空間的に可視化、定量解析することで多細胞解析に発展させる。また、生体内で癌細胞を標識する技術を確立することで、時空間的情報と分子情報を統合する手法の開発を目指す。

Outline of Final Research Achievements

Metastatic brain tumors have a poor prognosis and severely impact patients' quality of life, making it urgent to understand their pathology. We used two-photon microscopy to visualize lung cancer cells (metastatic brain tumors) and innate immune cells in the brain in vivo. Our findings revealed that lung cancer cells activate the brain's immune system and interact with the microenvironment during their establishment and disappearance. By conducting a temporal expression screening of these establishing cancer cells, we identified factors that allow cancer cells to evade elimination by the microenvironment. Among these, the expression of several “Don’t eat me” signals was found to increase cancer cell colonization rates, serving as key determinants in the metastatic process.

Academic Significance and Societal Importance of the Research Achievements

①領域横断性:肺癌転移性脳腫瘍への対応は呼吸器内科領域だが、疾患は脳神経領域に及び、専門とする研究者は少なかった。この両分野にまたがる、肺癌から転移性脳腫瘍への移行という過程を詳細に観察・記述し、分子機構の一部を明らかにした点で学術的意義がたかい。②転移性脳腫瘍は予後不良の疾患であり、いまだ特異的な治療法・予防法はない。申請者らの発見は、転移性脳腫瘍の発生段階に着目し、その進展・展開を防ぐ分子機構をひとつ見出しているため、これらの治療応用の可能性があり、社会的意義が高い。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (12 results)

All 2023 2022 2021

All Presentation (12 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results)

  • [Presentation] Interdisciplinary method to elucidate the interaction between brain microenvironment and cancer cells2023

    • Author(s)
      Takahiro Tsuji; Hiroaki Wake; Mariko Shindo; Rahadian Y. Hartantio; Misuzu Horikoshi; Daisuke Kato; Hiroaki Ozasa; Toyohiro Hirai
    • Organizer
      AACR Annual meeting 2023 in Orlando
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Heterogeneous microglial response to cancer cells visualized by in vivo imaging model2023

    • Author(s)
      Takahiro TSUJI, Mariko SHINDO, Daisuke KATO, Hiroaki WAKE
    • Organizer
      CSH Asia, Novel Insights into Glia Function & Dysfunction
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Heterogeneous microglial response to cancer cells visualized by in vivo imaging model2023

    • Author(s)
      Takahiro Tsuji; Mariko Shindo; Rahadian Y. Hartantio; MisuzuHorikoshi; Daisuke Kato; Hiroaki Wake
    • Organizer
      ISN-ESN meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生体内リアルタイムイメージングが可視化する脳内腫瘍微小環境の自然免疫応答2023

    • Author(s)
      辻 貴宏、和氣 弘明
    • Organizer
      バイオ・メディカル・フォーラム2024
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Microglial phagocytosis suppressed the development of metastatic tumors in the imaging model of brain metastasis2022

    • Author(s)
      Takahiro Tsuji, Hiroaki Wake, Mariko. Shindo, Daisuke Kato, Hiroaki Ozasa, Toyohiro Hirai
    • Organizer
      AACR Annual Meeting 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Microglial phagocytosis suppressed the development of metastatic tumors in the imaging model of brain metastasis2022

    • Author(s)
      辻貴宏、和氣弘明、進藤麻理子、加藤大輔、小笹裕晃、平井豊博
    • Organizer
      Neuro2022 (第45回神経科学大会)
    • Related Report
      2022 Research-status Report
  • [Presentation] In vivo Imaging of Cancer-Brain Immune Microenvironment Interactions2022

    • Author(s)
      Takahiro TSUJI, Mariko SHINDO, Rahadian Yudo HARTANTIO, Misuzu HORIKOSHI, Daisuke KATO, Hiroaki WAKE
    • Organizer
      第128回日本解剖学会総会・全国学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Visualizing the effect of 'don't eat me signal' on microglial anti-tumor activity by in vivo imaging of brain metastases2022

    • Author(s)
      辻貴宏、和氣弘明、進藤麻理子、加藤大輔、小笹裕晃、平井豊博
    • Organizer
      第127回日本解剖学会総会・全国学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Microglial phagocytosis suppressed the development of metastatic tumors in the imaging model of brain metastasis2022

    • Author(s)
      T. Tsuji, H. Wake, M. Shindo, D. Kato, H. Ozasa, T. Hirai
    • Organizer
      AACR Annual Meeting 2022
    • Related Report
      2021 Research-status Report
  • [Presentation] 転移性脳腫瘍の生体内可視化はミクログリアと癌細胞の相互作用の多様さを明らかにする2021

    • Author(s)
      Takahiro Tsuji, Hiroaki Wake, Mariko Shindo, Daisuke Kato, Hiroaki Ozasa, Toyohiro Hirai
    • Organizer
      第61回日本呼吸器学会学術講演会
    • Related Report
      2021 Research-status Report
  • [Presentation] Microglia phagocytose metastatic tumors and suppress metastasis formation2021

    • Author(s)
      Takahiro Tsuji, Hiroaki Wake, Mariko Shindo, Daisuke Kato, Hiroaki Ozasa, Toyohiro Hirai
    • Organizer
      第80回日本癌学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 転移性脳腫瘍モデルを用いた転移制御因子の探索2021

    • Author(s)
      辻貴宏、和氣弘明、進藤麻理子、加藤大輔、小笹裕晃、平井豊博
    • Organizer
      第62回日本肺癌学会学術講演会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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