Tissue Factor and Extracellular Vesicles: Activation of Coagulation and Impact on Survival in Cancer

SIMPLE SUMMARY: The tissue factor (TF)-factor VIIa complex is the major physiological initiator of blood coagulation. Tumors express TF and release TF-positive extracellular vesicles (EVs) into the circulation, and this is associated with the activation of coagulation. Circulating levels of EVTF activity may be a useful biomarker to identify patients at risk for thrombosis. Tumor TF and TF-positive EVs are also associated with reduced survival. ABSTRACT: Tissue factor (TF) is a transmembrane glycoprotein that functions as a receptor for FVII/FVIIa and initiates the extrinsic coagulation pathway. Tumors and cancer cells express TF that can be released in the form of TF positive (TF+) extracellular vesicles (EVs). In this review, we summarize the studies of tumor TF and TF + EVs, and their association with activation of coagulation and survival in cancer patients. We also summarize the role of tumor-derived TF + EVs in venous thrombosis in mouse models. Levels of tumor TF and TF + EVs are associated with venous thromboembolism in pancreatic cancer patients. In addition, levels of EVTF activity are associated with disseminated intravascular coagulation in cancer patients. Furthermore, tumor-derived TF + EVs enhance venous thrombosis in mice. Tumor TF and TF + EVs are also associated with worse survival in cancer patients, particularly in pancreatic cancer patients. These studies indicate that EVTF activity could be used as a biomarker to identify pancreatic cancer patients at risk for venous thrombosis and cancer patients at risk for disseminated intravascular coagulation. EVTF activity may also be a useful prognostic biomarker in cancer patients.