2011 Fiscal Year Final Research Report
The development of novel therapeutic strategies for targeting ovarian cancer stem cells
| Project/Area Number |
21390454
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2009 – 2011
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| 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 |
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| 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.
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[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
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Journal Title
Carcinogenesis
Volume: 32
Pages: 1597-1696
Peer Reviewed
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[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
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Journal Title
Cancer Cell
Volume: 19
Pages: 387-400
Peer Reviewed
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[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
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Journal Title
Peer Reviewed
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