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Elucidation of progression mechanism of malignant pleural mesothelioma using co-culture systems

Research Project

Project/Area Number 17K15569
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General physiology
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

MUKAI Satomi  愛知県がんセンター(研究所), 分子腫瘍学分野, 研究員 (10706146)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords悪性中皮腫 / 共培養 / 癌 / シグナル伝達
Outline of Final Research Achievements

Malignant mesothelioma is a highly aggressive tumor that mainly develops in the pleura and diffuses on the parietal and visceral pleura. To clarify the mechanisms by which the tumor diffuses throughout the pleura, we performed co-culture of normal mesothelial cells and malignant mesothelioma. As a result of examining various co-culture systems, it was suggested that normal mesothelial cells contributed to the growth promotion of malignant mesothelioma cells in the early stage of tumorigenesis in which normal mesothelial cells dominate. It was also suggested that the predominance of tumor cells would eliminate normal cells and replace them. In addition, it was revealed that the humoral factor released from malignant mesothelioma cells reduces the intercellular adhesion molecule of normal mesothelial cells.

Academic Significance and Societal Importance of the Research Achievements

近年、がん細胞と間質細胞との関連が注目されている。特に中皮細胞とがん細胞の関連ついては、卵巣癌や前立腺癌においてその腫瘍進展を促進させるという報告があるものの、周囲を中皮細胞に取り囲まれる悪性中皮腫についての知見は全くない。しかし本研究によって、悪性中皮腫細胞においても正常中皮細胞が腫瘍進展を促進させることが示唆された。今後さらなる解析により、その原因物質が同定されたあかつきには、それを標的とした新たな治療戦略を構築できる可能性が期待できる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2019 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Invited: 1 results)

  • [Journal Article] TAZ activation by Hippo pathway dysregulation induces cytokine gene expression and promotes mesothelial cell transformation.2019

    • Author(s)
      Matsushita A, Sato T, Mukai S, Fujishita T, Mishiro-Sato E, Okuda M, Aoki M, Hasegawa Y, Sekido Y
    • Journal Title

      Oncogene

      Volume: 38 Issue: 11 Pages: 1966-1978

    • DOI

      10.1038/s41388-018-0417-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] IL-1受容体拮抗薬はHippo経路の破綻した悪性中皮腫細胞の進展を抑制する2018

    • Author(s)
      向井 智美, 松下 明弘, 佐藤 龍洋, 藤下 晃章, 青木 正博, 関戸 好孝
    • Organizer
      第22回 日本がん分子標的治療学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] LATS2 inhibits O-GlcNAcylation in malignant mesothelioma cells.2018

    • Author(s)
      Satomi Mukai, Tatsuhiro Sato, Emi Mishiro-Sato, Masahiro Aoki, Norikazu Yabuta, Yoshitaka Sekido.
    • Organizer
      第77回 日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 悪性中皮腫におけるHippo経路の破綻による腫瘍進展機構2018

    • Author(s)
      向井 智美, 松下 明弘, 佐藤 龍洋, 藤下 晃章, 三城 恵美、奥田 真帆、青木 正博、関戸 好孝.
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Transcriptional coactivator TAZ induces malignant mesothelioma progression via enhancement of IL-1b transcription2017

    • Author(s)
      Satomi Mukai, Akihiro Matsushita, Tatsuhiro Sato, Teruaki Fujishita, Masahiro Aoki, Yoshitaka Sekido
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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