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Identification and analysis of novel metastasis regulators by the metastasis-step focused in vivo screening

Research Project

Project/Area Number 18K07216
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 InstitutionJapanese Foundation for Cancer Research

Principal Investigator

TAKEMOTO Ai  公益財団法人がん研究会, がん化学療法センター 基礎研究部, 主任研究助手 (20706494)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsがん転移 / in vivoスクリーニング
Outline of Final Research Achievements

Cancer metastasis is regulated by multi- and various steps. To understand the mechanism contributing to metastasis establishment and to propose the effective suppression strategy, analyses using the model possible to discriminate metastasis steps could be useful. Therefore, in this study, cancer cell lines lacking the specific metastasis step were used for in vivo screen, in which genome-wide shRNA library was transformed to each cell line and promoted metastatic frequency by the shRNA knock-down was monitored in vivo metastasis model. And then, identification of candidates of metastasis regulators and analysis using the specific model were performed in aiming to understand the novel metastasis-regulatory mechanism. Out of identified candidates, one was suggested to contribute in mobility and invasion ability important during the early metastasis step and the other in the regulation of expression of a platelet aggregation-promoting factor.

Academic Significance and Societal Importance of the Research Achievements

がん患者の死因の9割を超える転移に対して未だ効果的な抑制法が不足している現状において、転移制御因子の同定と各因子の機能に踏み込んだ詳細な解析による新規制御経路の理解と転移抑制標的としての妥当性の評価は、抑制法の提案に欠かせない。本研究では、機能解析を加速化できるように各転移過程にフォーカスしたin vivoスクリーニングを構築し、実際に複数の新規転移候補因子の同定と制御機構を示唆するに至った点で学術的意義がある。さらに、このような系によるスクリーニングの遂行と同定した因子のin vivoでの解析を進めることで効果的な転移抑制法開発の足掛かりとなる可能性がある。

Report

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

    (14 results)

All 2021 2020 2019 2018

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Novel knock-in mouse model for the evaluation of the therapeutic efficacy and toxicity of human podoplanin-targeting agents.2021

    • Author(s)
      Ukaji T, Takemoto A, Shibata H, Kakino M, Takagi S, Katayama R, Fujita N
    • Journal Title

      Cancer Science

      Volume: In press Issue: 6 Pages: 2299-2313

    • DOI

      10.1111/cas.14891

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A safety study of newly generated anti-podoplanin-neutralizing antibody in cynomolgus monkey (Macaca fascicularis).2018

    • Author(s)
      Ukaji T, Takemoto A, Katayama R, Takeuchi K, Fujita N
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 70 Pages: 33322-33336

    • DOI

      10.18632/oncotarget.26055

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Podoplanin - an emerging cancer biomarker and therapeutic target.2018

    • Author(s)
      Krishnan H, Rayes J, Miyashita T, Ishii G, Retzbach EP, Sheehan SA, Takemoto A, Chang YW, Yoneda K, Asai J, Jensen L, Chalise L, Natsume A, Goldberg GS.
    • Journal Title

      Cancer Sci.

      Volume: 印刷中 Issue: 5 Pages: 1292-1299

    • DOI

      10.1111/cas.13580

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 血小板活性化因子Podoplaninを介した腫瘍細胞社会ダイバーシティーの理解と制御2020

    • Author(s)
      高木聡, 片山量平, 宇梶太雄, 竹本愛, 藤田直也
    • Organizer
      第43回 日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 血小板活性化因子Podoplaninが作り出すがん免疫逃避環境の解析2020

    • Author(s)
      古賀美菜穂, 小池清恵, 藤田直也, 竹本愛, 片山量平, 高木聡
    • Organizer
      新学術領域「細胞第バース」第5回 公開シンポジウム ポスター発表
    • Related Report
      2020 Annual Research Report
  • [Presentation] Development of a humanized anti-podoplanin antibody inhibiting tumor-dependent platelet activation2019

    • Author(s)
      Ai Takemoto, Nobuhiko Gyobu, Mamoru Kakino, Shinya Fujihara, Naoki Goda, Junya Maeda, Miho Takami, Takao Ukaji, Satoshi Takagi, Ryohei Katayama, Kazue Tsuji-Takayama, Kenji Ichihara, Shinobu Nakayama, Yoshiyuki Ohsugi, and Naoya Fujita
    • Organizer
      The 24th JFCR-ISCC Symposium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Inhibition of Podoplanin-induced platelet activation for suppressing cancer progression2019

    • Author(s)
      Ai Takemoto
    • Organizer
      Cell Communication Disorders leading to Cancer and Other Diseases NLS seminar
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] ポドプラニン中和抗体による骨肉腫増殖抑制とその分子機構2019

    • Author(s)
      竹本愛、片山量平, 藤田直也
    • Organizer
      第23回日本がん分子標的治療学会
    • Related Report
      2019 Research-status Report
  • [Presentation] がん誘発性血栓症における腫瘍由来ポドプラニンの寄与2019

    • Author(s)
      竹本愛
    • Organizer
      第67回 日本心臓病学会学術集会/バイエル循環器病研究助成 第 26 回研究発表会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Targeting podoplanin-platelet interaction for the treatment of osteosarcoma2019

    • Author(s)
      Ai Takemoto, Takao Ukaji, Miho Takami, Shigeo Sato, Ryohei Katayama, Naoya Fujita
    • Organizer
      11th JCA-AACR Joint Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Targeting podoplanin-platelet interaction for suppressing tumor progression.2019

    • Author(s)
      Ai Takemoto, Takao Ukaji, Satoshi Takagi, Ryohei Katayama, Naoya Fujita
    • Organizer
      Podoplanin meeting 2019
    • Related Report
      2018 Research-status Report
  • [Presentation] 低転移性の結腸がん細胞を用いたin vivoスクリーニングによる新規がん転移制御因子の探索2018

    • Author(s)
      木村美紗, 藤田直也, 竹本愛
    • Organizer
      第22回 日本癌分子標的治療学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] がんと血小板の結合を標的とする化合物の探索と解析2018

    • Author(s)
      竹本愛, 片山量平, 藤田直也
    • Organizer
      第77回 日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] サルポドプラニンの血小板凝集誘導活性におけるPLAG4ドメインの役割2018

    • Author(s)
      宇梶太雄, 竹本愛, 藤田直也
    • Organizer
      第27回 日本がん転移学会学術集会
    • Related Report
      2018 Research-status Report

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

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