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Cervical cancer stem cell model derived from iPS cells to investigate new therapeutic targets

Research Project

Project/Area Number 16K11131
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionResearch Institute for Clinical Oncology, Saitama Cancer Center

Principal Investigator

Adachi Katsuyuki  埼玉県立がんセンター(臨床腫瘍研究所), 病院 婦人科, 副部長 (90735200)

Research Collaborator Kawana Kei  
Sato Masakazu  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords子宮頸癌 / iPSC / 組織幹細胞 / リザーブ細胞 / 個別化医療 / 癌幹細胞 / HPV / 誘導リザーブ細胞 / 子宮頸がん / 癌幹細胞モデル / 卵巣癌
Outline of Final Research Achievements

We established a reserve cell model that exists in SCJ from human iPS cells via intermediate mesoderm. The iPS cell-derived reserve cells expressed SCJ markers such as CK7, AGR2, CD63 and MMP7. When the culture conditions were changed, iPS cell-derived reserve cells were partially differentiated into squamous epithelium and partly into glandular epithelium. It is important findings that these cells are reserve cells. Then, cervical cancer stem cells into which HPV16 and HPV18 genes introduced were established. Based on the findings obtained in this study, establishing a cancer stem cell model for cervical cancer from the patient's own cell-derived iPS cells will lead to further personalized medicine.

Academic Significance and Societal Importance of the Research Achievements

子宮頸癌は婦人科悪性腫瘍の中で乳癌についで多い疾患である。近年では子宮頸癌検診の推進で早期でみつかる症例も増えているが、一方で再発症例については未だ治療の選択肢が少ない。一般的な化学療法だけではなく今後はより個別的な新規な治療開発が望まれているため、本研究は子宮頸癌の癌幹細胞に着目しその特徴から患者の個別化するための治療標的分子を見つけることに注力した。iPSCより子宮頸癌の癌幹細胞モデル樹立を目指し一部達成した。これは将来的には癌患者個人よりiPSCを樹立し、個別の子宮頸癌癌幹細胞モデルを使用し薬剤感受性テストやその他の治療感受性テストを行うことで個別化医療への応用が可能となると期待する。

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

All Journal Article (5 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 5 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (2 results) (of which Invited: 1 results)

  • [Journal Article] Intraperitoneal neutrophils activated by KRAS-induced ovarian cancer exert antitumor effects by modulating adaptive immunity.2018

    • Author(s)
      Yoshida M, Taguchi A, Kawana K, Ogishima J, Adachi K, Kawata A, Nakamura H, Sato M, Fujimoto A, Inoue T, Tomio K, Mori M, Nagamatsu T, Arimoto T, Koga K, Hiraike OW, Oda K, Kiyono T, Osuga Y, Fujii T.
    • Journal Title

      Int J Oncol

      Volume: 53(4) Pages: 1580-1590

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Therapeutic significance of targeting survivin in cervical cancer and possibility of combination therapy with TRAIL.2018

    • Author(s)
      Nakamura H, Taguchi A, Kawana K, Baba S, Kawata A, Yoshida M, Fujimoto A, Ogishima J, Sato M, Inoue T, Nishida H, Furuya H, Yamashita A, Eguchi S, Tomio K, Mori-Uchino M, Adachi K, Arimoto T, Wada-Hiraike O, Oda K, Nagamatsu T, Osuga Y, Fujii T.
    • Journal Title

      Oncotarget

      Volume: 9(17) Pages: 13451-13461

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Detachment from the primary site and suspension in ascites as the initial step in metabolic reprogramming and metastasis to the omentum in ovarian cancer.2018

    • Author(s)
      Sato M, Kawana K, Adachi K, Fujimoto A, Yoshida M, Nakamura H, Nishida H, Inoue T, Taguchi A, Ogishima J, Eguchi S, Yamashita A, Tomio K, Komatsu A, Wada-Hiraike O, Oda K, Nagamatsu T, Osuga Y, Fujii T.
    • Journal Title

      Oncol Lett.

      Volume: 15(1) Pages: 1357-1361

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Regeneration of cervical reserve cell-like cells from human induced pluripotent stem cells (iPSCs): class FormattedString { value: A new approach to finding targets for cervical cancer stem cell treatment }2017

    • Author(s)
      Sato M, Kawana K, Adachi K, Fujimoto A, Yoshida M, Nakamura H, Nishida H, Inoue T, Taguchi A, Ogishima J, Eguchi S, Yamashita A, Tomio K, Wada-Hiraike O, Oda K, Nagamatsu T, Osuga Y, Fujii T,
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 25 Pages: 40935

    • DOI

      10.18632/oncotarget.16783

    • URL

      https://localhost/en/publications/14e62492-5527-42a3-8ae6-5c3df1b66646

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Inhibition of endoplasmic reticulum (ER) stress sensors sensitizes cancer stem-like cells to ER stress-mediated apoptosis2016

    • Author(s)
      Fujimoto A, Kawana K, Taguchi A, Adachi K, Sato M, Nakamura H, Ogishima J, Yoshida M, Inoue T, Nishida H, Tomio K, Yamashita A, Matsumoto Y, Arimoto T, Wada-Hiraike O, Oda K, Nagamatsu T, Osuga Y, Fujii T.
    • Journal Title

      Oncotarget

      Volume: 7 Issue: 32 Pages: 51854

    • DOI

      10.18632/oncotarget.10126

    • URL

      https://pure.teikyo.jp/en/publications/844aa8cb-5d34-44df-8878-79efb846a9a6

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 癌幹細胞の個別化とそれに対応した個別化医療の開発~子宮頸癌を中心に2018

    • Author(s)
      足立 克之
    • Organizer
      第70回 日本産科婦人科学会学術講演会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 癌幹細胞の個別化とそれに対応した個別化医療の開発 ~子宮頸癌を中心に2018

    • Author(s)
      足立 克之
    • Organizer
      第70回 日本産科婦人科学会学術講演会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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