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Establishment and application of animal model of liver cancer stem cell using induced pluripotent stem cells

Research Project

Project/Area Number 16K07116
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionOkayama University

Principal Investigator

IWASAKI Yoshiaki  岡山大学, 保健管理センター, 教授 (00314667)

Co-Investigator(Kenkyū-buntansha) 笠井 智成  東京工科大学, 応用生物学部, 准教授 (30530191)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords肝がん / がん幹細胞 / 実験動物モデル / 人工多能性幹細胞 / 肝がん幹細胞 / 動物モデル
Outline of Final Research Achievements

Cancer stem cells were induced from mouse iPS cells by culturing in the presence of conditioned medium prepared from human hepatoma cell lines using a method that we have established. The cancer stem cells exhibited high tumorigenicity with rapid growth in immunodeficient mice. Primary cultured cells derived from this tumor were induced to differentiate into hepatocytes by a series of growth factors to produce liver cancer stem cell-like cells. Tumors formed by directly transplanting these cells into the livers of immunodeficient mice showed markers specific to liver cancer cells and also expression of factors related to stemness. However, only a part of tumors show differentiation to hepatocyte lineage, and it is necessary to establish more efficient animal models of liver cancer stem cells for detailed analysis of these cells.

Academic Significance and Societal Importance of the Research Achievements

進行肝がんの化学療法や放射線治療に対する治療抵抗性の原因としてのがん幹細胞の存在と、それを標的とした治療法の開発が注目されている。しかし、がん幹細胞をがん組織検体から分離して長期に維持することが難しく、そのため、がん幹細胞の詳しい解析は従来困難であった。本研究では、遺伝子操作を用いることなく、より自然な条件下で肝がん幹細胞モデルを作製することが出来た。さらに、iPS細胞を出発材料とすることから、種々の遺伝的背景を持つ試料の安定供給が可能となった。今後、より効率的な動物モデル作製法の開発により、がん幹細胞の詳細な病態解析及び薬剤耐性機序の解明に基づいた創薬が期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (7 results)

All 2018 2017 2016 Other

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

  • [Int'l Joint Research] ウェイン州立大学/インディアナ大学医学部(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] メヌーフィア大学(エジプト)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Up-Regulation of PI 3-Kinases and the Activation of PI3K-Akt Signaling Pathway in Cancer Stem-Like Cells Through DNA Hypomethylation Mediated by the Cancer Microenvironment2018

    • Author(s)
      Oo AKK, Calle AS, Nair N, Mahmud H, Vaidyanath A, Yamauchi J, Khayrani AC, Du J, Alam MJ, Seno A, Mizutani A, Murakami H, Iwasaki Y, Chen L, Kasai T, Seno M
    • Journal Title

      Transl Oncol

      Volume: 11 Issue: 3 Pages: 653-663

    • DOI

      10.1016/j.tranon.2018.03.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A cancer stem cell model as the point of origin of cancer-associated fibroblasts in tumor microenvironment2017

    • Author(s)
      Neha Nair, Anna Sanchez Calle, Maram Hussein Zahra, Marta Prieto-Vila, Aung Ko Ko Oo, Laura Hurley, Arun Vaidyanath, Akimasa Seno, Junko Masuda, Yoshiaki Iwasaki, Hiromi Tanaka, Tomonari Kasai, Masaharu Seno
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1

    • DOI

      10.1038/s41598-017-07144-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ヒトiPS細胞から作製するがん幹細胞モデル2016

    • Author(s)
      五味 真知、星川 健太、岩崎 良章、笠井 智成、妹尾 昌治
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] 胚様体形成させたiPS細胞から誘導するがん幹細胞2016

    • Author(s)
      古賀 めぐみ、Anna Sanchez Calle、岩崎 良章、笠井 智成、妹尾 昌治
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] がんの非ヒトモデル動物及びその作製方法、がん幹細胞及びその製造方法2016

    • Inventor(s)
      妹尾昌治、笠井智成、岩崎良章、大原利章、廣畑 聡、加来田博貴
    • Industrial Property Rights Holder
      国立大学法人 岡山大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016
    • Acquisition Date
      2017
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2022-02-21  

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