Development of novel therapeutic strategies for uterine leiomyoma

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11107
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kanazawa University
• Principal Investigator: Ono Masanori 金沢大学, 附属病院, 講師 (70348712)
• Co-Investigator(Kenkyū-buntansha): 丸山 哲夫 慶應義塾大学, 医学部(信濃町), 准教授 (10209702)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 子宮筋腫 / 子宮 / 組織幹細胞 / 子宮筋 / 子宮筋腫幹細胞

Outline of Final Research Achievements

Tissue-specific stem cells constitute a subset of cells residing in normal adult tissues. Estrogen and progesterone stimulate the growth of leiomyomas. Estrogen, together with its receptor ERα, enables progesterone action via induction of progesterone receptor expression. Progesterone induces the growth of leiomyoma by regulation of a set of key genes that control proliferation and apoptosis.The WNT/β-catenin pathway comprises a key component of this signaling system. The majority of medical treatments currently available for leiomyoma works by inhibiting estrogen or progesterone production or action, but tumors tend to regrow once treatment is stopped. We showed that uterine leiomyoma stem cells involve IGF2 and Insulin Receptor A. Targeting stem cells and their paracrine interactions with more differentiated cell populations within leiomyoma may lead to the development of more effective therapeutics for uterine leiomyoma.

Free Research Field

産婦人科学

Academic Significance and Societal Importance of the Research Achievements

子宮筋腫の発育に関わる因子として、これまで性ステロイド，Transforming growth factor-β/SMAD, Retinoic acid, PPARγが報告されてきた。今回我々は、ヒト子宮平滑筋の発生・分化・修復の機構とその異常、また子宮筋腫の病態メカニズムにWNT/β-cateninシグナル、IGF2とInsulin Receptor A のシグナルが関わっていることを明らかにした。これまで子宮筋腫の治療は性ステロイドに働きかけるものが使用され、使用終了後には子宮筋腫が増悪してしまっていたが、当研究成果によりは子宮筋腫の新たな効果的な治療薬開発に役立てることができる。