Role of cancer-derived extracellular vesicles in the extravasation of bladder cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16769
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Hirosaki University
• Principal Investigator: Yoneyama Mihoko 弘前大学, 医学研究科, 客員研究員 (50791696)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 細胞外小胞 / 膀胱癌 / 血管外脱出

Outline of Final Research Achievements

To examine the role of BCa cell-derived EVs for extravasation, we performed permeability test against human lung microvascular endothelial cell (HMVEC-L) monolayer. BCa cell-derived EVs treated HMVEC-L increased cell permeability. To confirm that the BCa cell derived EVs are responsible for the upregulation of cell endothelial permeability, we established that EVs secretion-decreased YTS-1 (TSGKD cells) cells by knocking down tumor susceptibility gene 101 (TSG101), which is well known as a regulator of EVs formation. The permeability of TSGKD cell treated HMVEC-L was significantly lower than when incubated with the control cells. In addition, lung metastasis capacity by using mouse tail vein injection model demonstrate that significantly reduced lung metastasis when injected TSGKD cells compared with control cells. Taken together, these results indicate BCa cell-derived EVs may contribute disruption of endothelial cells barrier for extravasation of BCa cells.

Free Research Field

泌尿器科学

Academic Significance and Societal Importance of the Research Achievements

癌細胞由来のEVs も癌転移のための微小環境形成に関わることが報告されているが、その機能・役割には、依然、未解明な点が多い。 本研究では、癌の血行性転移の鍵となる癌細胞の血管外脱出過程に焦点を絞り、癌細胞由来 EVs がこの過程で果たす役割を明らかにすることを目的しており、本研究を遂行することにより、多段階からなる血行性転移過程の全容解明に重要な貢献をすると考えられる。さらに血管透過性を亢進させる分子を同定することによって、この分子を標的とする治療法の開発につながり、社会的に大きな意義がある。