Abstract 611: Effect Of Tumor-derived Extracellular Vesicles On Platelet Function

Tumor-derived extracellular vesicles (EVs) have been described as pro-coagulant particles causing cancer-associated thrombosis. Tumor-derived EVs circulating in the bloodstream may interact with platelets or trigger the coagulation cascade, leading to venous and arterial thrombosis. In order to better understand the interaction of EVs with the hemostatic components, we aim to determine the mechanistic aspects of their interaction with platelets and their potential role in initiating coagulation. Given the wide variation of protein and integrin expression between different cancer cell types and the expectation of varying mechanistic effects, we have selected to study lung (A549), breast (MDA-MB-231) and glioblastoma (LN18) cell lines. We have characterized the effect of EVs derived from these cell lines on platelet function of aggregation and activation. Our data shows that both A549 and MDA-MB-231 EVs at 50 ug/mL significantly increase platelet aggregation as compared to control when incubated with the platelets for 10 min and in the presence of an agonist (ADP 20 uM) (Fig. 1). We confirmed the expression of phosphatidylserine on the surface of EVs using Annexin V and flow cytometry, indicating that they are pro-coagulant in nature. Furthermore, we will be investigating interaction of EVs with platelet receptor GP IIb-IIIa, agonist release, and presence of proteins such as Tissue Factor, as possible mechanisms for EV-induced platelet aggregation. Thus, the understanding of the mechanistic aspects behind the interaction between EVs and the hemostatic components could prove beneficial in the design of next generation agents for cancer-associated thrombosis. Figure 1. Platelet aggregation measured by light transmission aggregometry with ADP 20uM in the presence of A549 and MDA-MB-231 EVs (n=8 to 11)