Basic research on the mechanism of peritoneal dissemination of ovarian cancer and therapeutic strategies targeting the coagulation system

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09797
• 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: Kanazawa University
• Principal Investigator: Mizumoto Yasunari 金沢大学, 医学系, 講師 (00420331)
• Co-Investigator(Kenkyū-buntansha): 藤原 浩 金沢大学, 医学系, 教授 (30252456) ; 大黒 多希子 金沢大学, 学際科学実験センター, 教授 (30767249) ; 松岡 歩 金沢大学, 附属病院, 助教 (50579662)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 卵巣癌腹膜播種 / フィブリン網 / 組織因子 / 血管新生因子

Outline of Final Research Achievements

In this study, the involvement of fibrin networks and tissue factor (TF) in the establishment of ovarian cancer peritoneal seeding was clarified. The induction of replenishment vessels by angiogenic factor (VEGF-A) in the early stage of ovarian cancer cell clusters trapped in the fibrin network was suggested to be important. These results suggest the potential of therapeutic strategies such as antifibrin therapy, TF-targeted therapy, and antiangiogenic therapy in controlling peritoneal dissemination, a prognostic factor in ovarian cancer, and provide a basis for further validation.
Observations in a peritoneal seeding model using normal-immunized mice reproduced the trapping of cancer cell clusters by a fibrin network similar to that observed in human clinical specimens, providing a useful model for further analysis.

Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究で明らかとなった卵巣癌腹膜播種の成立におけるフィブリン網、組織因子、血管新生因子の関与は、これまでの上皮間葉転換（EMT）仮説とは全く異なる機序であり、卵巣がんの予後不良因子である腹膜播種に対する、新たな治療戦略の開発への礎となりうるものである。早期発見の困難な卵巣高異形度漿液性癌における新規治療戦略に結実する可能性があり、社会的意義が大きいと考えられる。