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. ABSTRACT: 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.