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

• 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
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• 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 / 血管新生 / 癌関連繊維芽細胞 / 卵巣癌 / 腹膜播種 / 凝固系カスケード / fibrin網

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.

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。

Research Products

• [Journal Article] Novel strategy of ovarian cancer implantation: Pre-invasive growth of fibrin-anchored cells with neovascularization. (2019)
  • Author(s): Matsuoka A, Mizumoto Y, Ono M, Kagami K, Obata T, Terakawa J, Maida Y, Nakamura M, Daikoku T, Fujiwara H.
  • Journal Title: Cancer Sci. Volume: 110 Issue: 8 Pages: 2658-2666
  • DOI: 10.1111/cas.14098
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 卵巣癌腹膜播種機構を再考察するー新しい播種形成機序の提言ー (2019)
  • Author(s): 松岡歩、水本泰成、小野政徳、鏡京介、小幡武司、寺川純平、 毎田佳子、中村充宏、大黒多希子、藤原浩
  • Organizer: 第21回北陸GOG Open clinical conference
• [Patent(Industrial Property Rights)] 卵巣癌の検出方法及び卵巣癌治療剤 (2019)
  • Inventor(s): 藤原浩
  • Industrial Property Rights Holder: 藤原浩
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019
  • Acquisition Date: 2019