Fibrinolytic Activity of Circulating Microvesicles Is Associated with Progression of Breast Cancer

Abstract

The fibrinolytic system plays an important role in breast cancer, favoring progression through extracellular-matrix degradation, angiogenesis, apoptosis and cellular proliferation. The expression of urokinase-type plasminogen activator (uPA) in breast cancer tissue is widely recognized as an unfavorable prognostic factor. However, fibrinolytic activity associated with uPA cannot be reliably measured in the blood because of the rapid inhibition of uPA by plasminogen activator inhibitor-1 (PAI-1). By contrast, circulating microvesicles (Mvs) in peripheral blood protect bound enzymes from inhibition. Mvs are extracellular vesicles, released from various types of cells, and their size fluctuates between 100 and 1,000 nm. Mvs carry DNA, RNA, miRNA, and proteins, thereby serving as a source of horizontal communication between cells. We investigated whether fibrinolytic activity on circulating Mvs reflects breast cancer progression. The study population consisted of 13 patients with breast cancer and 13 healthy women. The cancer patients included 4 patients in remission, 3 patients with locally advanced cancer, and 6 with metastatic disease. Mvs were isolated from peripheral blood, quantified by a protein concentration method, and their fibrinolytic potential was measured by their capacity to generate plasmin. Although the quantity of Mvs found in patients with cancer and healthy individuals was similar, plasmin generated on Mvs was twice the amount in patients with metastasis than in healthy women (P < 0.05), underlying the value of this distinctive parameter. The data suggest that in breast cancer patients, higher fibrinolytic activity of circulating Mvs could be related to progression and metastasis of breast cancer.

Keywords: breast cancer; cancer progression; fibrinolytic activity; microvesicles; urokinase-type plasminogen activator.