Prothrombotic Effects of Prostasomes Isolated from Prostatic Cancer Cell Lines and Seminal Plasma

Abstract

Thromboembolism is well recognized as a major complication of cancer. Many tumor cells overexpress tissue factor (TF), which activates blood coagulation in cancer patients. Inflammatory cells expressing TF are also contributors to this activation. In prostate cancer, we believe that prostasomes may also be involved in the initiation of blood coagulation. Prostasomes are submicron secretory granules derived from the prostate gland. They are surrounded by membrane and their extracellular appearance and membrane architecture are complex. Seminal prostasomes are believed to be necessary for successful fertilization and act as protectors of the spermatozoa in the lower and upper female genital tract. Cells from prostate cancer and its metastases are able to produce and export prostasomes to the extracellular environment. These prostasomes may differ quantitatively rather than qualitatively from their normal counterparts with regard to protein composition and function. A majority of human prostate cancers have been found to overexpress TF, and we have demonstrated by various methods that prostasomes derived from prostate cancer cells express considerably higher levels of TF compared with prostasomes of nonmalignant cell origin. The mechanism related to thromboembolic disease generated by prostasomes in prostatic cancer patients may be the early release of prostasomes from prostate cancer cells into the blood circulation, where they will evoke their blood-clotting effects.

Risk of thromboembolic disease in men with prostate cancer undergoing androgen deprivation therapy

“…Nonetheless, previous surgeries and disease progression are strongly associated with an increased risk of TED and should be accounted for when assessing the impact of ADT on TED [1][2][3][4][5][6][7][8][9][10]. In our previous study, we observed an increased risk of TED in men with PCa on ADT compared with the general Swedish male population, although a number of health and lifestyle factors could not be accounted for [2].…”

“…Surgery and disease severity are known to increase the risk of thromboembolic disease (TED) in men with prostate cancer (PCa) [1][2][3][4][5][6][7][8][9]. The risk of TED is further enhanced in men with PCa treated with androgen deprivation therapy (ADT) [1,2,10,11]; however, it is unknown to what extent ADT influences the risk of TED when accounting for previous surgeries and disease progression.…”

Risk of thromboembolic diseases in men with prostate cancer: results from the population-based PCBaSe Sweden

“…Babiker and colleagues 37 showed that the early release of prostasomes from prostate cancer cells into the circulation might evoke blood-clotting effects causing thromboembolic disease. Another study by Li and colleagues 16 showed a possible link between endocrine treatment and thromboembolic disease, in which they noted that the prevention of experimental arterial thrombosis by the use of androgens at physiological concentrations is mediated by the androgen receptor through modulation of platelet activation.…”

Pathogenesis, clinical and laboratory aspects of thrombosis in cancer

“…Cells from prostate cancer and its metastases both produce and release prostasomes, which differ quantitatively rather than qualitatively from their normal counterparts. As in other cancers, human prostate carcinoma constitutively overexpress TF and prostasomes derived from these cancer cells vehicle larger amounts of TF [18]. A similar mechanism, involving TF-bearing microvesicles that arise from tumor cells or monocytes, characterizes the thrombophilic state of patients with other types of cancer [14,19,20].…”