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2011 Fiscal Year Final Research Report

The development of novel therapeutic strategies for targeting ovarian cancer stem cells

Research Project

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Project/Area Number 21390454
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKumamoto University

Principal Investigator

KATABUCHI Hidetaka  熊本大学, 大学院・生命科学研究部, 教授 (90224451)

Co-Investigator(Kenkyū-buntansha) TASHIRO Hironori  熊本大学, 医学部附属病院, 特任准教授 (70304996)
MOTOHARA Takeshi  熊本大学, 医学部附属病院, 医員 (10457591)
Project Period (FY) 2009 – 2011
Keywords上皮性卵巣癌 / 癌幹細胞 / 卵巣表層上皮 / 卵巣癌治療 / 卵巣癌モデル
Research Abstract

Emerging evidence suggests that human cancers arise from normal stem cells, and are composed of hierarchies of cells sustained by tumor-initiating cells(T-ICs), conceptually termed cancer stem cells(CSCs). Epithelial cell adhesion molecule(EpCAM) is a type I transmembrane glycoprotein that is expressed specifically in epithelial tissues and is overexpressed in some epithelial cancers. In normal tissues, EpCAM is expressed in several types of epithelial stem/progenitor cells and contributes to tissue development. On the other hand, a subpopulation of EpCAM-positive cells has been identified as CSCs in some human cancers. In the light of these considerations, we evaluated the EpCAM-positive cells for their stem cell properties in adult mouse ovary, and established the ovarian T-ICs by introduction of defined genetic elements in EpCAM-positive cells. EpCAM-positive cells possess the hallmarks of somatic stem cells and CSCs in this mouse model of ovarian tumorigenesis. Furthermore, our experimental mouse model facilitates further studies toward a comprehensive understanding of normal stem cells and CSCs in ovary. Ultimately, such studies will be imperative to define whether eradication of ovarian CSCs is critical for effective therapy.

  • Research Products

    (16 results)

All 2011 2010 2009

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (7 results)

  • [Journal Article] Transient depletion of p53 followed by transduction of c-Myc and K-Ras converts ovarian stem-like cells into tumor-initiating cells2011

    • Author(s)
      T. Motohara, S. Masuko, T. Ishimoto, T. Yae, N. Onishi, T. Muraguchi, A. Hirao, Y. Matsuzaki, H. Tashiro, H. Katabuchi, H. Saya, O Nagano
    • Journal Title

      Carcinogenesis

      Volume: 32 Pages: 1597-1696

    • Peer Reviewed
  • [Journal Article] Mutual contribution of Pten and estrogen to endometrial carcinogenesis in a PtenloxP/loxP mouse model2011

    • Author(s)
      F. Saito, H. Tashiro, Y. To, H. Ohtake, T. Ohba, A. Suzuki, H. Katabuchi
    • Journal Title

      Int J Gynecol Cancer

      Volume: 21 Pages: 1343-1349

    • Peer Reviewed
  • [Journal Article] Short RNA duplexes elicit RIG-I-mediated apoptosis in a cell type-an. d length-dependent manner2011

    • Author(s)
      O. Ishibashi, MM. Ali, SS. Luo, T. Ohba, H. Katabuchi, T. Takeshita, T. Takizawa
    • Journal Title

      Science Signaling

      Volume: 4(198) Pages: 74

    • Peer Reviewed
  • [Journal Article] CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth2011

    • Author(s)
      T. Ishimoto, O. Nagano, T. Yae, M. Tamada, T. Motohara, H. Oshima, M. Oshima, T. Ikeda, R. Asaba, H. Yagi, T. Masuko, T. Shimizu, T. Ishikawa, K. Kai, E. Takahashi, Y. Imamura, Y. Baba, M. Ohmura, M. Suematsu, H. Baba, H. Saya
    • Journal Title

      Cancer Cell

      Volume: 19 Pages: 387-400

    • Peer Reviewed
  • [Journal Article] Involvement of M2-polarized macrophages in the ascites from advanced epithelial ovarian carcinoma in tumor progression via Stat3 activation2010

    • Author(s)
      K. Takaishi, Y. Komohara, H. Tashiro, H. Ohtake, T. Nakagawa, H. Katabuchi, M. Takeya
    • Journal Title

      Cancer Sci

      Volume: 101 Pages: 2128-2136

    • Peer Reviewed
  • [Journal Article] Immunohistochemical analysis of 17β-hydroxysteroid dehydrogenase isozymes in human ovarian surface epithelium and epithelial ovarian carcinoma2010

    • Author(s)
      K. Motohara, H. Tashiro, Y. Taura, T. Ohba, H. Katabuchi
    • Journal Title

      Med Mol Morphol

      Volume: 43 Pages: 197-203

    • Peer Reviewed
  • [Journal Article] Long-term oncological outcomes of ovarian serous carcinomas with psammoma bodies : A novel insight into the molecular pathogenesis of ovarian epithelial carcinoma2010

    • Author(s)
      T. Motohara, H. Tashiro, Y. Miyahara, I. Sakaguchi, H. Ohtake, H. Katabuchi
    • Journal Title

      Cancer Science

      Volume: 101 Pages: 1550-1556

    • Peer Reviewed
  • [Journal Article] Gene expression profile for predicting survival in advanced-stage serous ovarian cancer across two independent datasets2010

    • Author(s)
      K. Yoshihara, A. Tajima, T. Yahata, S. Kodama, H. Fujiwara, M. Suzuki, Y. Inishi, M. Hatae, K. Sueyoshi, H. Fujiwara, Y. Kubo, K. Kotera, H. Tashiro, H. Katabuchi, I. Inoue, K. Tanaka
    • Journal Title

      PLoS ONE

      Pages: 9615

    • Peer Reviewed
  • [Journal Article] Oncogenic transformation of human ovarian surface epithelial cells with defined cellular oncogenes2009

    • Author(s)
      R. Sasaki, M. Narisawa-Saito, T. Yugawa1, M. Fujita, H. Tashiro, H. Katabuchi, T. Kiyono
    • Journal Title

      Carcinogenesis

      Volume: 30 Pages: 423-431

    • Peer Reviewed
  • [Presentation] Lecture : Molecular Carcinogenesis in Ovarian Cancer「Epithelial ovarian carcinogenesis : What we have learned from human ovarian surface epithelial cells?」2011

    • Author(s)
      H. Katabuchi
    • Organizer
      The 12th Japan-Korea Joint Conference of Obstetrics and Gynecology
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2011-08-31
  • [Presentation] Long-term oncological outcomes of ovarian serous carcinomas with psammoma bodies2011

    • Author(s)
      T. Motohara, H. Tashiro, H. Ohtake, R. Honda, T. Ohba, H. Katabuchi
    • Organizer
      The 50th annual congress of Taiwan Association of Obstetrics and Gynecology
    • Place of Presentation
      Kaohsiung
    • Year and Date
      2011-03-12
  • [Presentation] Identification of EpCAM as a marker for somatic stem-like cells and cancer stem cells in mouse models of ovarian tumorigenesis2011

    • Author(s)
      T. Motohara, O. Nagano, H. Tashiro, H. Saya, H. Katabuchi
    • Organizer
      1^<st> Asan Kumamoto-Joint Symposium on Gynecologic Cancer
    • Place of Presentation
      Seoul、Korea
    • Year and Date
      2011-02-19
  • [Presentation] Lecture「Epithelial ovarian cancer toward the novel therapeutic strategy」2010

    • Author(s)
      H. Katabuchi
    • Organizer
      Zhejiang University-Kumamoto University Life Science Symposium
    • Place of Presentation
      Hangzhou, China
    • Year and Date
      2010-12-13
  • [Presentation] Lecture : Molecular Targeted Therapy of Ovarian Cancer「Putative precursor cells, risk factors, and molecular mechanisms of its carcinogenesis」2010

    • Author(s)
      H. Katabuchi
    • Organizer
      Asian Society of Gynecologic Oncology 1st International Workshop on Gynecologic Oncology
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2010-08-01
  • [Presentation] Lecture「Pathophysiological dynamics of human ovarian surface epithelial cells in epithelial ovarian cancer」risk factors, and molecular mechanisms of its carcinogenesis」2009

    • Author(s)
      H. Katabuchi
    • Organizer
      The 13th Japan-Korea Joint Meeting for Gynecological Pathology
    • Place of Presentation
      Damyang, Korea
    • Year and Date
      2009-09-19
  • [Presentation] Special lecture「A new tool to investigate the tumorigenesis and therapeutic modalities of epithelial ovarian cancer」2009

    • Author(s)
      H. Katabuchi
    • Organizer
      The Inaugural Symposium of Asan Cancer Center
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2009-04-01

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Published: 2013-07-31  

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