Archive | 2021
Role of tissue-factor bearing extracellular vesicles released from ovarian cancer cells in platelet aggregation in vitro and venous thrombosis in mice
Abstract
Abstract Objective Venous thromboembolism (VTE) contributes to morbidity and mortality in women with ovarian cancer. Underlying mechanisms of venous thrombosis in ovarian cancer are not well-understood. The aim of this study was to identify the potential role of tissue factor (TF)-bearing extracellular vesicles (EVs) originated from cancer cells in venous thrombosis in ovarian cancer models. Methods We examined the expression of TF on EVs generated by ovarian cancer cells and the effect of TF-positive EVs on platelet aggregation. Furthermore, we performed TF-knockdown or induced TF-overexpression in ovarian cancer cell lines and examined the effects of EVs obtained from these cells on platelet aggregation. We examined the effect of TF-bearing EVs originated from ovarian cancer cells on venous thrombosis in a mouse model of inferior vena cava (IVC) stenosis. Results TF was expressed in several ovarian cancer cell lines. EVs derived from ovarian cancer cell lines expressing TF promoted platelet aggregation. TF-knockdown in TF-high CAOV3 and OVCAR8 ovarian cancer cells delayed platelet aggregation induced by their EVs in vitro. Conversely, TF overexpression in TF-low A2780 and HeyA8 cells shortened platelet aggregation time induced by their EVs. EVs from TF-overexpressing A2780\xa0\u200bcells enhanced thrombosis formation in the IVC stenosis model and resulted in a larger clot burden as compared to EVs from A2780 control cells. Conclusions TF expression in ovarian cancer cell-derived EVs promoted platelet aggregation and thrombosis in preclinical models. These findings may have implications for reducing VTE rates in women with ovarian cancer.