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

Cancers

Bernhard Moser¹  JohannesA. Schmid¹  Lena Hell²  Lisa-Marie Mauracher²  Cihan Ay²  Thomas Däullary²  Ella Grilz²  Vanessa Burghart²  Johannes Thaler²  Ingrid Pabinger²  Gero Kramer³ 

[1] Center for Physiology and Pharmacology, Institute of Physiology, Medical University of Vienna, 1090 Vienna, Austria;Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria;Department of Urology, Medical University of Vienna, 1090 Vienna, Austria;

关键词: prostate cancer;    disseminated intravascular coagulation;    tissue factor;    extracellular vesicles;    peripheral blood mononuclear cells;    platelets;   

DOI  :  10.3390/cancers13071487

来源: DOAJ

【 摘 要 】

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 showed 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.

【 授权许可】

Unknown