Novel Mechanism of Cancer Thrombosis Induced by Microvesicles

Abstract

Microvesicles consist of a heterogeneous array of cell-derived vesicles of different origins. A subset of microvesicles, termed microparticles, are derived from budding from cell surfaces, whereas the smaller exosomes are released from the endosomal compartment through specific cellular transport mechanisms.1–3 All cells, both nontransformed and malignant, release microvesicles, with increased numbers released in response to inflammatory stimuli, apoptosis, and other sources of cellular stress. Though the enumeration of microvesicles in plasma remains challenging,4 plasma microvesicle concentrations are thought to range from 107 to 1011/mL. See accompanying article on page 772 Although microvesicles mediate many biological effects, there has been great interest in their role in thrombotic disease.5 Because thrombosis is a common complication in patients with cancer,6 cancer-associated thrombosis (CAT) has been a productive area in which to study the prothrombotic activity of microvesicles. Several studies have investigated the prothrombotic mechanisms of microvesicles derived from cancer cells and patients with cancer, many focusing on the role of tissue factor (TF).7 Some studies have identified a correlation between the expression of TF by microvesicles from cancer patients and the development of clinical thrombosis.8–10 However, though these correlations seem to be significant in the case of pancreatic cancer, they have not been confirmed in other cancer types.11 Indeed, the …