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The roles of senescence-related exosomes in the lung cancer microenvironment

Research Project

Project/Area Number 19K17649
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionJikei University School of Medicine

Principal Investigator

Fujita Yu  東京慈恵会医科大学, 医学部, 講師 (10737133)

Project Period (FY) 2019-04-01 – 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: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsエクソソーム / 特発性肺線維症 / 肺がん / SASP / microRNA / 老化 / COPD / IPF
Outline of Research at the Start

COPDとIPFはいずれも加齢が発症危険因子である老化関連肺疾患であり、高率に肺がんを合併する難治性疾患である。近年、100nm前後の細胞外小胞であるエクソソームは、新たな細胞間情報伝達物質として注目されており、老化細胞から分泌されるエクソソームはSASPとしての特徴を有して、COPDやIPFの病態、さらには合併するがんの微小環境制御や悪性化に深く関わっている可能性が考えられる。本研究は、老化細胞由来エクソソームの肺がんに対する役割を解明し、エクソソームに注目した新規バイオマーカーによる病態評価及びこれら難治性肺疾患合併肺がんの治療戦略の確立を目的とする。

Outline of Final Research Achievements

Idiopathic pulmonary fibrosis (IPF) was reported to be associated with increased risk of lung cancer as a result of the occurrence of atypical or dysplastic epithelial changes in fibrosis which progressed to invasive malignancy. Although exosomes, a type of extracellular vesicles (EVs), have emerged as new players in intercellular communication, their role in the function of senescent cell secretome in the IPF pathogenesis has been largely unexplored. Here, we found the roles of senescence-related exosomes in the lung cancer microenvironment. To elucidate the mechanisms of lung cancer development through senescent-related exosome transfer will lead to a new therapy against IPF and lung cancer.

Academic Significance and Societal Importance of the Research Achievements

IPFは、進行性の難治性疾患であり肺がんを効率に合併する。現状これらの病態の理解は不足しており、肺線維化とがん悪性化の関連性がエクソソームで解明されることで、新しい治療法に繋がることが期待される。IPFは、世界的に見ても死亡率の高い疾患であり、新規治療法が開発されれば、その社会的意義は十分大きいものと考えられる。

Report

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

    (5 results)

All 2021 2020

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (2 results) (of which Invited: 2 results)

  • [Journal Article] Intercellular Communication by Vascular Endothelial Cell-Derived Extracellular Vesicles and Their MicroRNAs in Respiratory Diseases2021

    • Author(s)
      Fujimoto Shota、Fujita Yu、Kadota Tsukasa、Araya Jun、Kuwano Kazuyoshi
    • Journal Title

      Frontiers in Molecular Biosciences

      Volume: 7 Pages: 619697-619697

    • DOI

      10.3389/fmolb.2020.619697

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chaperone-mediated autophagy receptor modulates tumor growth and chemoresistance in non-small cell lung cancer2020

    • Author(s)
      Ichikawa A, Fujita Y, Hosaka Y, Kadota T, Ito A, Yagishita S, Watanabe N, Fujimoto S, Kawamoto H, Saito N, Yoshida M, Hashimoto M, Minagawa S, Hara H, Motoi N, Yamamoto Y, Ochiya T, Araya J, Kuwano K.
    • Journal Title

      Cancer Sci

      Volume: 111 Issue: 11 Pages: 4154-65

    • DOI

      10.1111/cas.14629

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extracellular Vesicles from Fibroblasts Induce Epithelial-Cell Senescence in Pulmonary Fibrosis2020

    • Author(s)
      Kadota Tsukasa、Yoshioka Yusuke、Fujita Yu、Araya Jun、Minagawa Shunsuke、Hara Hiromichi、Miyamoto Atsushi、Suzuki Souichiro、Fujimori Sakashi、Kohno Tadasu、Fujii Takeshi、Kishi Kazuma、Kuwano Kazuyoshi、Ochiya Takahiro
    • Journal Title

      American Journal of Respiratory Cell and Molecular Biology

      Volume: 63 Issue: 5 Pages: 623-636

    • DOI

      10.1165/rcmb.2020-0002oc

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Small RNAおよびエクソソームを用いた 難治性呼吸器疾患における病態解明と治療法開発2021

    • Author(s)
      藤田雄
    • Organizer
      第61回日本呼吸器学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 肺線維化に対する気道上皮細胞由来エクソソームを用いた新規治療戦略2020

    • Author(s)
      藤田雄
    • Organizer
      第60回日本呼吸器学会学術講演会若手シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited

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Published: 2019-04-18   Modified: 2025-11-20  

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