Extracellular Vesicle-Associated Tissue Factor Activity in Prostate Cancer Patients with Disseminated Intravascular Coagulation

Simple Summary Disseminated intravascular coagulation (DIC) may occur in patients with advanced prostate cancer. In the present study, we detected elevated extracellular vesicle (EV)-associated tissue factor (TF) activity in the plasma of prostate cancer patients with DIC compared with matched prostate cancer patients without DIC and healthy individuals. TF-exposing EVs from DIC patients were highly coagulant in a clotting assay. In in vitro co-culture experiments, EV-TF activity was increased by interactions between a TF-exposing prostate cancer cell line (DU145), peripheral blood mononuclear cells (PBMCs), and platelets. Data from this study contribute to the understanding of the pathogenesis of prostate cancer-related DIC. Patients with advanced prostate cancer may develop fulminant disseminated intravascular coagulation (DIC). Circulating extracellular vesicles (EVs)-exposing tissue factor (TF), the initiator of the coagulation cascade, may play an important role. We included 7 prostate cancer patients with DIC, 10 age- and stage-matched cancer controls without DIC, and 10 age-matched healthy male individuals. EV-TF activity was highly elevated in prostate cancer patients with DIC (11.40 pg/mL; range: 4.34-27.06) compared with prostate cancer patients without DIC (0.09 pg/mL; range: 0.00-0.30, p = 0.001) and healthy controls (0.18 pg/mL; range: 0.09-0.54; p = 0.001). Only EVs from patients with DIC reduced fibrin clot formation time of pooled plasma in a TF-dependent manner. Next, we performed in vitro co-culture experiments including EVs derived from a prostate cancer cell line with high (DU145) and low (LNCaP) TF expression, peripheral blood mononuclear cells (PBMCs), and platelets. Co-incubation of DU145 EVs with PBMCs and platelets significantly increased EV-TF activity in conditioned medium and induced TF activity on monocytes. No such effects were seen in co-culture experiments with LNCaP EVs. In conclusion, the findings indicate that elevated EV-TF activity plays a role in the development of prostate-cancer-related DIC and may result from interactions between tumor-derived EVs, monocytes, and platelets.