Procoagulant Circulating Microparticles In Health And Disease Essay

Procoagulant Circulating Microparticles In Health And Disease Essay Procoagulant Circulating Microparticles In Health And Disease â€" Essay Example > Procoagulant Circulating MicroparticlesNormal cells and cancer cells release microparticles and exosomes into their environment. Microparticles are budded off from the cell surface and are best known for their ability to support coagulation. Exosomes, which are stored in intracellular multivesicular bodies and are released when the membrane of the multivesicular body fuses with the cells plasma membrane, efficiently modulate the immune response. (Kakkar, DeRuvo, Chinswangwatanakul, Tebbutt, Williamson, 2005 p. 1004-5) Dvorak and coworkers demonstrated that tumor-derived procoagulant activity (PCA) is associated with sedimentable, ultramiscroscopic plasma membrane-derived vesicles in vitro (cancer cell-conditioned culture medium) as well as in vivo (ascitis tumor fluid from animals). These vesicles, isolated by centrifugation at 100 000 · g, ranged in size from 15 and 800 nm (median 60 nm) (Dvorak, Quay, Orenstein, Bitzer, Carvalho, 2007 p. 923-4) These investigators showed that c ancer cell-derived vesicles support coagulation via various mechanisms, i.e. one procoagulant activity associated with shed tumor vesicles behaved as tissue factor, and shed tumorvesicles also acted at a second step late in the clotting cascade at the level of prothrombinase generation, presumably by providing a phospholipid surface(Dvorak, Quay, Orenstein, Bitzer, Carvalho, 2007 p. 923-4). A decade later, in 1993, from four cases of Trousseaus syndrome, i.e. cancer patients who have spontaneous recurrent or migratory episodes of venous thrombosis, arterial emboli due to nonbacterial thrombotic endocarditis, or both, it was concluded that two properties of a tumor can account for the pathogenesis of Trousseaus syndrome: The first is that the malignant cell expresses tissue factor on its external surface. The second is that the tumor cells are anatomically positioned so that cells or vesicles shed from them are exposed to the circulating blood, either directly or by their entrance i nto the circulatory system from the lymphatic system. (Rapaport, 2005 p. 153-61)Concurrently, other investigators concluded that a continuing entrance into the circulation of tissue factor from malignant cells is responsible for the manifestations of Trousseaus syndrome in most patients. (Rapaport, 2005 p. 153-61) Taken together, these studies demonstrate that the strong association between malignant disease and coagulation activation mayâ€" at least partially â€" be explained by the release of tissue factor (TF) exposing vesicles from cancer cells into the blood or other body fluids, which in turn may contribute to the low grade disseminated intravascular coagulation and thrombotic episodes which are characteristic of Trousseaus syndrome. Other potential sources of TF-exposing vesiclesThe true cellular origin of microparticle-associated TF in cancer patients, however, has proven surprisingly difficult to establish. Patients with disseminated breast and pancreatic cancer have incr eased levels of microparticle-associated TF in plasma compared with controls, and the patients with a low likelihood of survival have (in plasma) both a high microparticle-associated TF activity and increased numbers of epithelial mucin (MUC1) exposing microparticles. (Rapaport, 2005 p. 153-61)Whether or not MUC1-exposing microparticles, for example microparticles originating from tumor cells, expose TF, however, was not investigated. Surprisingly, a low number of microparticles was present that stained positive for both MUC1 and glycoprotein IIIa (CD61; integrin b3). As glycoprotein IIIa is abundantly exposed on platelets and platelet-derived microparticles, they concluded that a small part of circulating microparticles seemed to result from fusion of cellular vesicles originating from malignant epithelial cells and platelets. Whether or not these particular microparticles expose TF, however, was not investigated.