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Elucidation of the mechanism of dormant cancer cells in cholangiocarcinoma

Research Project

Project/Area Number 21K08725
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 InstitutionTohoku University

Principal Investigator

Kunihiro Masuda  東北大学, 医学系研究科, 大学院非常勤講師 (30569645)

Co-Investigator(Kenkyū-buntansha) 川口 桂  東北大学, 大学病院, 助教 (10700164)
青木 修一  東北大学, 大学病院, 助教 (30844451)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords胆道癌 / Fbxw7 / 休眠がん細胞 / FBXW7 / 胆管癌 / 癌幹細胞 / がん幹細胞
Outline of Research at the Start

胆管癌の転移再発や治療抵抗性に関与する休眠がん細胞を同定し,分子機構を関与を解明し,新規治療標的に発展させることである.
休眠がん細胞は時間を経た再発転移機構であり,この仕組みに癌幹細胞(CSC)の関与が示されている.細胞周期の休止期に存在し,従来の化学療法に抵抗性を示す.Fbxw7は多くの癌で不活性型変異を認める癌抑制遺伝子で,血液癌や固形癌でFBXW7を介したCSCの制御が報告された.
本研究はFbxw7による休眠がん細胞の制御メカニズムを解明し,治療標的にするという胆管癌の新たな治療戦略に発展させることを目的とする.

Outline of Final Research Achievements

We conducted experiments to elucidate the regulatory mechanism of dormant cancer cells by Fbxw7 and to develop a new therapeutic strategy for cholangiocarcinoma by targeting the dormant cancer cells as therapeutic targets.Dormant cancer cells are a time-course mechanism of recurrent metastasis, and cancer stem cells (CSCs) have been shown to be involved in this mechanism. Fbxw7 is a tumor suppressor gene, and FBXW7-mediated regulation of CSCs has been reported in hematological and solid tumors.We examined the expression of FBXW7 and CSC-related molecules in resected cholangiocarcinoma specimens after chemotherapy,and found no correlation between treatment efficacy and their expression, and could not clarify their association.

Academic Significance and Societal Importance of the Research Achievements

胆管癌の転移再発や治療抵抗性に関与する休眠がん細胞を同定し,分子機構を関与を解明し,新規治療標的に発展させることである.
休眠がん細胞は時間を経た再発転移機構であり,この仕組みに癌幹細胞(CSC)の関与が示されている.細胞周期の休止期に存在し,従来の化学療法に抵抗性を示す.Fbxw7は多くの癌で不活性型変異を認める癌抑制遺伝子で,血液癌や固形癌でFBXW7を介したCSCの制御が報告された.
本研究はFbxw7による休眠がん細胞の制御メカニズムを解明し,治療標的にするという胆管癌の新たな治療戦略に発展させることを目的とする.しかしながら,免疫染色上両者の発現に相関はなく,関連性は認めなかった.

Report

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

    (1 results)

All 2023

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

  • [Journal Article] Collagen XVII regulates tumor growth in pancreatic cancer through interaction with the tumor microenvironment2023

    • Author(s)
      Kashiwagi Ryosuke、Funayama Ryo、Aoki Shuichi、Matsui Aya、Klein Sebastian、Sato Yukihiro、Suzuki Tsubasa、Murakami Keigo、Inoue Koetsu、Iseki Masahiro、Masuda Kunihiro、Mizuma Masamichi、Naito Hisamichi、Duda Dan G.、Unno Michiaki、Nakayama Keiko
    • Journal Title

      Cancer Science

      Volume: 114 Issue: 11 Pages: 4286-4298

    • DOI

      10.1111/cas.15952

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research

URL: 

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

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