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Research on targeted therapy of pancreatic cancer stem cells using exosomes

Research Project

Project/Area Number 18K08627
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionKagoshima University

Principal Investigator

MATSUBARA Shyuichiro  鹿児島大学, 医学部, 客員研究員 (60199841)

Co-Investigator(Kenkyū-buntansha) 新地 洋之  鹿児島大学, 医歯学域医学系, 教授 (60284874)
高尾 尊身  鹿児島大学, 医歯学総合研究科, 客員研究員 (80171411)
下野 隆一  香川大学, 医学部, 准教授 (60404521)
Project Period (FY) 2018-04-01 – 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 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords癌幹細胞 / 膵臓癌 / CD133 / nTOR / Akt / CD13 / エクソゾーム / microRNA / mTOR / KRAS / マクロピノサイトーシス / 繊維化
Outline of Final Research Achievements

Using pancreatic cancer stem-like model cells with high CD133 expression level, we studied for target molecules and their mechanisms of action for exosome-based therapies. The involvement of the serine / threonine kinase mTOR was elucidated. mTOR works by forming two distinct complexes mTORC1 (mTOR complex 1) and mTORC2 (mTOR complex 2), which are involved in cancer stem cell maintenance through different actions, and the combined inhibition of mTORC1 and the mTORC2→Akt pathway, which affects on mTORC1 through a feedback mechanism, is effective in suppressing cancer stem cells.

Academic Significance and Societal Importance of the Research Achievements

膵癌は5年生存率が10%前後の難治性のがんで、新たな治療法が求められている。治療の障害となる再発・転移は腫瘍を作る幹細胞、癌幹細胞によって引き起こされると考えられ、癌幹細胞の根絶を目的とした標的療法が注目される。また、膵癌などKRASが活性化した細胞では細胞外小胞の一種エクソゾームの取り込みが亢進しており、膵癌治療の運搬体としてエクソゾームの利用が試みられている。米国のKalluri, R. らは変異型KRASを標的として研究をすすめているが、この方法ではエクソゾームの取り込み自体が低下する懸念がある。mTOR、Aktの同時阻害はこれの回避が期待できる。

Report

(7 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (5 results)

All 2020 2019 2018

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (3 results)

  • [Journal Article] Prevention of Akt phosphorylation is a key to targeting cancer stem-like cells by mTOR inhibition2020

    • Author(s)
      Shyuichiro Matsubara, Koichiro Tsukasa, Taisaku Kuwahata, Sonshin Takao
    • Journal Title

      Human cell

      Volume: 33 Issue: 4 Pages: 1197-1203

    • DOI

      10.1007/s13577-020-00416-9

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Significance of glucose transporter 1 (GLUT-1) expression in the therapeutic strategy for pancreatic ductal adenocarcinoma2018

    • Author(s)
      Kurahara H, Maemura K, Mataki Y, Sakoda M, Iino S, Kawasaki Y, Arigami T, Mori S, Kijima Y, Ueno S, Shinchi H, Natsugoe S.
    • Journal Title

      Ann Surg Oncol

      Volume: 25 Issue: 5 Pages: 1432-1439

    • DOI

      10.1245/s10434-018-6357-1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Prevention of Akt phosphorylation is a key to targeting pancreatic cancer stem-like cells by mTORC1 inhibition.2020

    • Author(s)
      Matsubara, S., Shimono, R., Furukawa, T., Takao, S.
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Differential functions of mTORC1 and mTORC2 in the maintenance of stem-like properties of pancreatic cancer cells2019

    • Author(s)
      Matsubara, S., Tsukasa, K., Kuwabata, T., Obara, T., Matsuyama,T., Takao, S.
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Differential functions of mTORC1 and mTORC2 in the maintenance of stem-like properties of pancreatic cancer cells2018

    • Author(s)
      Matsubara, S., Tsukasa, K., Kuwabata, T., Obara, T., Matsuyama, T., Takao, S.
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2025-01-30  

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