Ovarian cancer exosome-mediated evasion of the anti-angiogenic effect of bevacizumab

Abstract Objective Is there a way for ovarian cancer to escape the antiangiogenic effects of bevacizumab Methods Bevacizumab treatment of different types of tumor cells altered the content of VEGF-A both inside and outside the cells.HUVEC endothelial cells were treated with conditioned supernatant and subjected to angiogenesis, proliferation and migration phenotype assays.The exosome release inhibitor GW4869 was used to treat the supernatant, and then the endothelial cell phenotype experiment was performed to verify the role of exosomes in the supernatant. After disrupting the exosome membrane structure, the content of VEGF-A in the supernatant was detected.The exosomes in the supernatant were extracted by the kit, and the VEGF-A content in the exosomes was detected. Database, PCR and WB were used to verify the differential expression of molecules related to cargo sorting such as CD82 in cells treated with bevacizumab. Immunofluorescence was used to verify the co-localization of CD82 and VEGF-A. Results VEGF-A content in and outside ovarian cancer cells increased after tumor cells were treated with bevacizumab. Ovarian cancer cell-derived conditioned supernatant can promote angiogenesis, proliferation and migration phenotype of HUVEC, and these effects may be achieved by exosomes. Ovarian cancer may capture VEGF-A by exosomes mediated by CD82, transmit VEGF-A to downstream endothelial cells and promote their angiogenesis, migration and proliferation to achieve the evading effect of bevacizumab. Conclusion CD82 may mediate the capture of VEGF-A by ovarian cancer exosomes to escape the anti-angiogenic effect of bevacizumab.