Tumor Shedding and Coagulation

Abstract

Three syngeneic carcinomas from two species shed plasma membrane vesicles when cultured in vitro or grown in the ascites tumor form in vivo. Shed vesicles carry procoagulant activity that can account for the activation of the clotting system and the fibrin deposition associated with these and many other types of malignancy in animals and man.

Role of extracellular membrane vesicles in the pathogenesis of various diseases, including cancer, renal diseases, atherosclerosis, and arthritis

“…In Trousseau's syndrome, there is a marked increase in circulating, procoagulant microvesicles, and these MVs are mostly derived by shedding from the outer plasma membranes of malignant tumor cells themselves. 30,68 The main procoagulant factor in tumor-generated microvesicles appears to be TF which, in Trousseau's syndrome, activates platelets, causing them to aggregate and initiate thrombosis of major (large-sized) veins and arteries. In Trousseau's syndrome, widespread thromboembolism becomes the dominant feature of the patient's cancer-related illness, and often serves as the cause of death.…”

“…They usually measure from 100 to 500 nm in diameter, and are released by budding from the surface membranes of activated platelets, after platelet attachment to endothelial-lined inner surfaces of the vessel wall, during normal hemostasis 62 (Table 2). First referred to as 'platelet dust,' circulating MVs are CD 42 positive (indicating their origin from platelets) and contain platelet-derived tissue factor (TF) and von Willebrand's factor (VWF), 30,63 which are the major initiators of intravascular coagulation in normal processes and in thromboembolic diseases. 30 Platelet release of extracellular MPs also increases during the tightly regulated process of platelet apoptosis, and is dependent on the formation of mitochondrial permeability transition pore.…”

“…First referred to as 'platelet dust,' circulating MVs are CD 42 positive (indicating their origin from platelets) and contain platelet-derived tissue factor (TF) and von Willebrand's factor (VWF), 30,63 which are the major initiators of intravascular coagulation in normal processes and in thromboembolic diseases. 30 Platelet release of extracellular MPs also increases during the tightly regulated process of platelet apoptosis, and is dependent on the formation of mitochondrial permeability transition pore. 64 Disseminated intravascular coagulation (DIC) is a very prevalent, often fatal disorder, that occurs as a complication of various medical conditions, including septicemia, metastatic cancer, and ischemic cardiovascular disease.…”

Therapeutic and diagnostic applications of extracellular vesicles

“…These vesicles were mainly composed of phospholipids and appeared to promote blood clothing [1] and cartilage calcification [2]. In the decades that followed, using electron microscopy imaging, vesicular structures could be visualized in calf serum [3] and the first observations were made on tumor cellderived membrane vesicles [4]. Initially it was assumed that the observed vesicles were solely released by outward budding of the cell membrane.…”

Antibody response of nude (RNU/RNU) and hairy (RNU/+) rats to circulating cell surface components from human pancreatic cancer xenografts

“…There is evidence with animal tumours that this process may also occur in the host during tumour growth in vivo (Calafat et al, 1976;Dvorak et al, 1981;Warenius et al, 1981). If this phenomenon is also a feature of human tumour growth in nude animals it may offer a biological selection which can be exploited in the production of monoclonal antibodies with some selectivity for the cancer cell surface.…”