Novel strategy of ovarian cancer implantation, Preinvasive growth of fibrin anchored cells with neovascularization

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16762
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Kanazawa University
• Principal Investigator: Matsuoka Ayumi 金沢大学, 附属病院, 医員 (50579662)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: Tissue factor / 腹膜外血管新生 / 中皮細胞層 / 癌細胞集塊 / 卵巣癌腹膜播種

Outline of Final Research Achievements

We identified a different strategy for the peritoneal invasion of Ovarian cancer cells mass (OCM). As an early step, the OCM anchor in the extraperitoneal fibrin networks and induce the migration of CD34‐positive and VEGFA‐positive endothelial cells, constructing extraperitoneal vascular networks. During the extraperitoneal growth of OCM, podoplanin‐positive and αSMA‐positive CAF appears. In more advanced lesions, the boundary line of mesothelial cells disappears around the insertion areas of feeding vessels and extraperitoneal and intraperitoneal stroma are integrated, enabling the OCM to invade the host stroma, being associated with CAF. In addition, tissue factors are strongly detected around these peritoneal implantation sites and their levels in ascites were higher than that in blood. These findings demonstrate a novel strategy for peritoneal invasion of ovarian cancer and TF‐targeted intraperitoneal anti‐cancer treatment.

Free Research Field

Gynecologic Oncology

Academic Significance and Societal Importance of the Research Achievements

今回腹膜転移部位の詳細な観察により,「Fibrin網による癌細胞集塊のtrap,それを足場に新生血管や間質組織を周りに構築し成育し, 浸潤する」というこれまでと異なる観点での播種形成機構が考えられた。組織の再構築や修復で重要な凝固系機構が播種形成の初期から関与しており, Tissue factorをatrgetとした癌微小環境の制御は卵巣癌腹膜播種の制御に対する治療に結びつく可能性がある。