Development of therapy that targets ovarian clear cell carcinoma stem cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24501313
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kyoto Prefectural University of Medicine (2013-2014); The University of Tokyo (2012)
• Principal Investigator: NASU Ryo 京都府立医科大学, 医学(系)研究科(研究院), 助教 (30466859)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 癌 / 癌幹細胞 / 卵巣明細胞癌 / CD133 / Wntシグナル / LGR5

Outline of Final Research Achievements

Clear cell carcinoma of the ovary (CCC) has the worst prognosis among epithelial ovarian cancers because of its chemoresistance. In this study, we tried to develop a new therapy that targets CCC stem cells. We analyzed the gene expression profile of CCC stem cells established by our group and found the high expression of the stem cell marker LGR5. Moreover, we analyzed the molecular mechanisms of the activation of Wnt signaling by the R-spondin-LGR5 axis and found that R-spondin/Wnt stimuli activate Wnt signaling via promoting novel phosphorylation of Axin1. Thus, both antibodies that target the extracellular domain of LGR5 and small molecules that inhibit Axin1 phosphorylation hold promise as novel anti-tumor reagents.

Free Research Field

腫瘍生物学