The role of microvesicles in the hyper-coagulation associated with prostate cancer

Abstract

Patients with prostate cancer (PC) are at high risk of developing migratory thrombosis compared to healthy individuals. This is due to the haemostatic abnormality as a result of the presence of cancer, and is referred to as Trousseau’s syndrome. Trousseau's syndrome leads to increased mortality among cancer patients, and is considered the second cause of death after cancer itself. We investigated the role of microvesicles (MVs), which are circular membrane compartments shed from cancer as well as from healthy cells, in the development of Trousseau’s syndrome. We compared the pro-coagulant activities between MVs derived from PC cell lines with different oncogenic and metastatic characteristics, using chromogenic assays to determine their thrombin generation. Microvesicles from the more aggressive DU145vIII and more metastatic PC3-MLN4 show increased thrombin generation compared to MVs derived from DU145 and PC3. We also compared thrombin generation in MVs extracted from plasma of PC patients of various cancer stages. MVs from PC patients with a metastasized tumour had increased thrombin generation compared to patients with localized tumours. Finally, we transfected the CHO cell line with the human protease-activated receptor 1 (hPAR1), the principal receptor of thrombin. PC MVs led to the activation of PAR1 in CHO (hPAR1), indicating thrombin generation. Our in vitro studies suggest a potential role of PC MVs in the migratory thrombosis observed in Trousseau’s syndrome, due to their independent ability to generate active thrombin. We also demonstrated that thrombin generation of PC-derived MVs correlated with the oncogenic and metastatic characteristics of prostate cancer.