Role of angiogenesis and its inhibition in the surrounding myometrium for the development of uterine leiomyoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09219
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Chiba University
• Principal Investigator: Ishikawa Hiroshi 千葉大学, 大学院医学研究院, 講師 (70553973)
• Co-Investigator(Kenkyū-buntansha): 生水 真紀夫 千葉大学, 大学院医学研究院, 教授 (30226302)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 子宮筋腫 / 血管内皮成長因子 / 低酸素

Outline of Final Research Achievements

We identified the highest expression of mRNA of vascular endothelial growth factor (VEGF) and its receptors, VEGFR1 and VEGFR2, in myometrial tissues surrounding uterine leiomyoma, so called leiomyoma pseudocapsule, compared with that in normal myometrium and uterine leiomyoma, suggesting that angiogenesis in the leiomyoma pseudocapsule may play important roles for the blood supply to the leiomyoma. We also identified the growth of leiomyoma xenograft was significantly inhibited by the administration of the inhibitors of hypoxia-inducible factor-1(HIF-1), which expression is higher in uterine leiomyoma than that in myometrium, in non-obese diabetes/severe combined immunodeficient mice. Because inhibition of angiogenesis in the leiomyoma pseudocapsule may induce downregulation of HIF-1 in uterine leiomyoma, these results suggest that inhibition of HIF-1 is a potential therapeutic strategy for the treatment of uterine leiomyoma.

Free Research Field

産婦人科学

Academic Significance and Societal Importance of the Research Achievements

子宮筋腫は産婦人科で最も多い腫瘍で、女性の3人に1人が罹患すると言われているが、その病態はいまだ解明されていない。現在の子宮筋腫に対する薬物療法は女性ホルモンの作用を遮断してしまうため、6か月以上の長期間の投与が認められておらず、新しい治療法の開発が求められている。
本研究で明らかとなった子宮筋腫周囲筋層の血管新生阻害効果は、女性のホルモンバランスを崩さない新しい子宮筋腫の治療法の開発につながると考えられる。