Development of a novel therapeutic strategy for intraperitoneal dissemination of ovarian cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K24054
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Keio University
• Principal Investigator: Ueno Sayaka 慶應義塾大学, 医学部(信濃町), 訪問研究員 (80848937)
• Project Period (FY): 2019-08-30 – 2022-03-31
• Keywords: 卵巣癌 / 腹腔内免疫 / 転移 / 再発 / BET阻害剤 / 腹腔内マクロファージ

Outline of Final Research Achievements

We identified pigment epithelium-derived factor (PEDF) as a promoting factor of OC dissemination. PEDF functions through induction of CD206-positive IL-10-producing macrophages. High PEDF expression in tumors was associated with shorter overall survival and disease-free survival in OC patients. Concentrations of PEDF in ascites and serum were significantly higher in OC patients than those with more benign tumors and correlated with recurrence within 2 years. These data suggest that PEDF might serve as a prognostic biomarker. Bromodomain and extraterminal (BET) inhibitors reduce PEDF expression and limit both OC cell survival and CD206positive macrophage induction in the peritoneal cavity. Together, we identified PEDF as a driver of OC dissemination, and a BET protein-PEDF-IL-10 axis as a promising therapeutic target for OC.

Free Research Field

卵巣癌

Academic Significance and Societal Importance of the Research Achievements

本研究で、卵巣がんの腹腔内播種に関わる新たな因子であるPEDFを同定することができた。 また、PEDFの発現制御メカニズムが明らかになったことで、卵巣がん播種の治療に効果が見込まれる薬剤を同定することができた。さらにPEDFが再発予測マーカーとして臨床応用できる可能性を示唆する結果が得られた。これらの知見は、今後の卵巣がん治療開発に利用できる可能性がある。