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Dynamics of GMN cancer cells: Synergistic effect on cancer malignant alteration by CAF

Research Project

Project/Area Number 19K07681
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionAkita University

Principal Investigator

Itoh Go  秋田大学, 医学系研究科, 助教 (60607563)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsCAF / 細胞分裂 / がん微小環境 / 浸潤 / サイトカイン / 癌関連線維芽細胞 / 上皮間葉転換 / 染色体分配 / 細胞質分裂 / 染色体不安定性 / ゲノム不安定性 / 癌浸潤 / 多核・巨核癌細胞
Outline of Research at the Start

(1)GMN癌細胞由来のサイトカインもしくは、細胞外小胞に含まれる分子がNF (正常線維芽細胞) のCAF化や活性化へと繋がるメカニズムを解明する。
(2)CAF由来の細胞外小胞や液性因子によるGMN癌細胞のEMT、腫瘍浸潤の加速メカニズムを解明する。
(3)1と2のメカニズムの関与分子とヒト癌症例での腫瘍の悪性度、治療後再発との関連を検討する。

Outline of Final Research Achievements

Giant / Multi-Nucleated cancer cells (GMN cancer cells) are found in tumor tissues after chemotherapy or radiation therapy. GMN cancer cells are by no means quiescent cells. GMN cancer cells were found to contribute to active alteration of the tumor microenvironment and to be susceptible to mesenchymal transition from their feedback. GMN cancer cells and CAF (Cancer associated fibroblasts) mobilization, which seemingly different phenomena, will lead to creation of a new field of research. This study, which elucidates the signaling pathways of GMN cancer cell proliferation and cancer infiltration / metastasis, will lead to the creation of drugs and tumor markers that block and detect cancer recurrence and malignancy after cancer treatment.

Academic Significance and Societal Importance of the Research Achievements

癌細胞における細胞分裂の失敗は、癌ゲノム情報に大規模な変異を与える(ミクロ的変化)。また、癌細胞とその周辺細胞との相互作用も癌細胞の性質変異につながる(マクロ的変化)。ミクロとマクロな2つの変化が連携し、癌悪性化を増幅させるメカニズムを明らかにできる。従来とは異なる効果的な癌抑制経路を模索し、癌の緩和を目指している。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (17 results)

All 2022 2021 2020 2019

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 2 results) Presentation (7 results)

  • [Journal Article] Cancer-associated fibroblasts educate normal fibroblasts to facilitate cancer cell spreading and T cell suppression.2022

    • Author(s)
      Go Itoh, Kurara Takagane, Yuma Fukushi, Sei Kuriyama, Michinobu Umakoshi, Akiteru Goto, Kazuyoshi Yanagihara, Masakazu Yashiro, Masamitsu Tanaka
    • Journal Title

      Molecular Oncology

      Volume: -

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SKAP2 suppresses inflammation-mediated tumorigenesis by regulating SHP-1 and SHP-2.2022

    • Author(s)
      Kurara Takagane, Michinobu Umakoshi, Go Itoh, Sei Kuriyama, Akiteru Goto, Masamitsu Tanaka
    • Journal Title

      Oncogene

      Volume: -

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pigment Epithelium Derived Factor is involved in the late phase of osteosarcoma metastasis by increasing extravasation and cell-cell adhesion.2022

    • Author(s)
      Sei Kuriyama, Gentaro Tanaka, Kurara Takagane, Go Itoh, Masamitsu Tanaka
    • Journal Title

      Frontiers in Oncology

      Volume: -

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of asporin reprograms cancer cells to acquire resistance to oxidative stress.2021

    • Author(s)
      Yuto Sasaki, Kurara Takagane, Takumi Konno, Go Itoh, Sei Kuriyama, Kazuyoshi Yanagihara, Masakazu Yashiro, Satoru Yamada, Shinya Murakami, Masamitsu Tanaka
    • Journal Title

      Cancer Science

      Volume: -

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamics of Myosin II Filaments during Wound Repair in Dividing Cells.2021

    • Author(s)
      Md Istiaq Obaidi Tanvir, Go Itoh, Hiroyuki Adachi, Shigehiko Yumura
    • Journal Title

      Cells

      Volume: -

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chromosome alignment-maintaining phosphoprotein CHAMP1 plays a role in cell survival through regulating Mcl-1 expression.2021

    • Author(s)
      Maho Hino, Kenji Iemura, Masanori Ikeda, Go Itoh, Kozo Tanaka
    • Journal Title

      Cancer Science

      Volume: -

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of asporin reprograms cancer cells to acquire resistance to oxidative stress2021

    • Author(s)
      Sasaki Y, Takagane K, Konno T, Itoh G, Kuriyama S, Yanagihara K, Yashiro M, Yamada S, Murakami S, Tanaka M.
    • Journal Title

      Cancer Sci

      Volume: 112 Issue: 3 Pages: 1251-61

    • DOI

      10.1111/cas.14794

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ca2+-Calmodulin Dependent Wound Repair in Dictyostelium Cell Membrane2020

    • Author(s)
      Md.Shahabe Uddin Talukder, Mst. Shaela Pervin, Md. Istiaq Obaidi Tanvir, Koushiro Fujimoto, Masahito Tanaka, Go Itoh, Shigehiko Yumura
    • Journal Title

      Cells

      Volume: 9(4):1058 Issue: 4 Pages: 1058-1058

    • DOI

      10.3390/cells9041058

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dynamin-Like Protein B of Dictyostelium Contributes to Cytokinesis Cooperatively with Other Dynamins.2019

    • Author(s)
      Fujimoto K, Tanaka M, Rana AYKMM, Jahan MGS, Itoh G, Tsujioka M, Uyeda TQP, Miyagishima SY, Yumura S.
    • Journal Title

      Cells

      Volume: 26 Pages: 8-8

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Macrophage-mediated transfer of cancer-derived components to stromal cells contributes to establishment of a pro-tumor microenvironment.2019

    • Author(s)
      Umakoshi M, Takahashi S, Itoh G, Kuriyama S, Sasaki Y, Yanagihara K, Yashiro M, Maeda D, Goto A, Tanaka M.
    • Journal Title

      Oncogene

      Volume: 38 Pages: 2162-2162

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 癌微小環境における巨大癌細胞の動態2021

    • Author(s)
      伊藤剛・八代正和・田中正光
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 腫瘍進行における巨核・多核癌細胞の動態2021

    • Author(s)
      伊藤剛・福士由真・田中正光
    • Organizer
      第39回染色体ワークショップ・第19回核ダイナミクス研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Dynamics of giant cancer cells cooperating with cancer associated fibroblasts2020

    • Author(s)
      Itoh Go, Tanaka Masamitsu
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] マクロファージ、CAF、癌細胞が協調したMMP9産生と活性化および、癌への関与2019

    • Author(s)
      伊藤剛、佐々木裕都、高金くらら、田中正光
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 間質細胞と協調した巨大癌細胞の増殖と癌浸潤ジオメトリー2019

    • Author(s)
      伊藤剛、田中正光
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] CAFにより教育された線維芽細胞はがんの播種を促進する2019

    • Author(s)
      田中正光、伊藤剛、高金くらら、八代正和
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 癌関連マクロファージの産生するMMP9が癌浸潤を促進するメカニズムについて2019

    • Author(s)
      伊藤剛、中村華子、佐々木裕都、田中正光
    • Organizer
      第85回日本生化学学会・東北支部例会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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