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Elucidation of cancer progression mechanism associated with novel forms of cell death in pancreatic cancer using organoid models

Research Project

Project/Area Number 18K08708
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 InstitutionKyushu University

Principal Investigator

MORIYAMA Taiki  九州大学, 大学病院, 准教授 (70586859)

Co-Investigator(Kenkyū-buntansha) 寅田 信博  九州大学, 大学病院, 臨床検査技師 (00398075)
大内田 研宙  九州大学, 大学病院, 講師 (20452708)
鬼丸 学  九州大学, 医学研究院, 共同研究員 (80529876)
水元 一博  九州大学, 大学病院, 准教授 (90253418)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords膵癌 / 細胞死 / necroptosis / オルガノイド / 微小環境 / 膵癌オルガノイド / 細胞死形態 / 癌微小環境
Outline of Final Research Achievements

Necroptosis is a form of programmed cell death that is accompanied by release of intracellular contents. We investigated the significance of necroptosis in pancreatic cancer.
RIP3 and MLKL are highly expressed in human pancreatic cancer tissues. CXCL5 released from necroptotic cells promotes cancer cell migration and invasion via CXCR2 in pancreatic cancer cells. Induction of necroptosis is a possible therapeutic strategy to overcome apoptosis resistance in pancreatic cancer, but it could also enhance cancer progression. Development of necroptosis induction therapy might include a means of suppressing its negative influences.

Academic Significance and Societal Importance of the Research Achievements

本研究では、特に癌の進展に大きく影響を与えていると考えられる、プログラムされた細胞死のひとつであるnecroptosisに注目した。
本研究結果から、膵癌の薬物治療において、apoptosis耐性となった癌細胞にnecroptosisを誘導することが有効である可能性が示唆されたとともに、タンパク発現の差異によってnecroptosis誘導への反応性が異なることや、necroptosisによって放出された因子が癌の進展を促進することが明らかとなった。necroptosisが誘導される条件や放出される因子を抑制する戦略をさらに研究することで、膵癌に対する新たな治療戦略の開発につながると考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2020 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (6 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Necroptosis in pancreatic cancer promotes cancer cell migration and invasion by release of CXCL52020

    • Author(s)
      Yohei Ando, Kenoki Ohuchida , Yoshiki Otsubo, Shin Kibe, Shin Takesue, Toshiya Abe, Chika Iwamoto, Koji Shindo, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Takao Ohtsuka, Yoshinao Oda, Masafumi Nakamura
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 1 Pages: e0228015-e0228015

    • DOI

      10.1371/journal.pone.0228015

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 微小環境因子依存性に基づいた膵癌subtype分類および薬物治療抵抗性についての検討2020

    • Author(s)
      新川智彦、大内田研宙、奥田翔、大坪慶志輝、岩本千佳、進藤幸治、仲田興平、大塚隆生、中村雅史
    • Organizer
      第75回日本消化器外科学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Subtype classification of pancreatic ductal adenocarcinoma based on microenvironmental niche factors dependency and chemotherapy resistance2020

    • Author(s)
      Shinkawa T, Ohuchida K, Iwamoto C, Shindo K, Nakata K, Ohtsuka T, Nakamura M
    • Organizer
      14th World Congress of International Hepeto-Pancreato-Biliary Association
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] R-spondin依存膵癌オルガノイド形成に関わる膵星細胞由来微小環境因子の検索2020

    • Author(s)
      新川智彦、大内田研宙、持田郁己、久野恭子、奥田翔、大坪慶志輝、岩本千佳、進藤幸治、 森山大樹、仲田興平、永井俊太郎、大塚隆生、中村雅史
    • Organizer
      第120回日本外科学会定期学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Necroptosis in Pancreatic Cancer Promotes Cancer Cell Migration and Invasion by Release of CXCL52019

    • Author(s)
      Ando Y, Ohuchida K, Otsubo Y, Sagara A, Kibe S, Takesue S, Nakayama M, Shindo K, Moriyama T, Nakata K, Ohtsuka T, Mizumoto K, Nakamura M
    • Organizer
      The 50th Annual Meeting of the American Pancreatic Association(APA)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 膵癌細胞への異なった細胞死誘導による遊走・浸潤能への影響の比較2019

    • Author(s)
      安藤陽平、大内田研宙、岐部晋、武居晋、中山宏道、森山大樹、仲田興平、宮坂義浩、大塚隆生、中村雅史
    • Organizer
      第74回日本消化器外科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 膵癌細胞のnecroptosisによって放出されるCXCL5は膵癌細胞の遊走・浸潤を促進する2019

    • Author(s)
      安藤陽平, 大内田研宙, 相良亜希子, 米永晃子, 岐部晋, 武居晋, 中山宏道, 森山大樹, 仲田興平, 宮坂義浩, 大塚隆生, 水元一博, 中村雅史
    • Organizer
      第119回日本外科学会定期学術集会
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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