Chemotherapeutic Drugs Increase the Release of Procoagulant Microparticles from Cancer Cells (2010)

Undergraduate: Yemeng Lu

Faculty Advisor: Nigel Mackman
Department: Biology

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Compared to the general population, people afflicted with cancer have a 4 fold increase for developing venous thromboembolism (VTE), clots in the deep veins of the legs or the pulmonary artery of the lung. The ones receiving chemotherapy treatment have a 6 to 7 fold increase. However, the mechanistic pathways through which chemotherapeutic drugs produce a prothrombotic (tendency to form clots) state in veins are poorly understood. Tissue factor (TF) is a receptor that is expressed constitutively on cells surrounding the blood vessel. It functions as the primary initiator in the blood coagulation cascade. Increased TF in the blood can lead to thrombosis in cancer patients. Besides TF expression on the surface of extravascular cells, TF can be found circulating in the blood in the form of Microparticles (MPs), which are small membrane vesicles released by apoptotic (programmed death) and activated cells. Tumors cells exposed to chemotherapeutic agents release MPs and have been found to constitutively express TF on their cell surface. The results of my study show that after chemotherapeutic treatments, tumor cells release TF-positive MPs. The increased level of circulating TF would initiate clotting and lead to a prothrombotic state in patients treated with chemotherapy.