Local and systemic activation of blood coagulation appears to be a common and an important host response to growing tumors. The pathogenesis of this process and the importance of the resultant fibrin deposition to tumor growth remains uncertain. Tumor cells, tumor-associated macrophages and tumor-associated endothelial cells contain proteins with potent procoagulant activities (PCAs) and fibrin deposition has been observed histologically on the surface of both tumor cells and stromal elements within tumors in situ. It is the objective of this project to examine this association in more detail and, using specific probes, to define the importance of the 2 main types of PCAs in the pathogenesis of fibrin deposition in human cancer. Utilizing specific monoclonal antibodies (mAbs) and cDNA probes specific for the PCAs, cell surface antigens and immunoregulatory molecules, we will examine the interactions between the 2 principal tumor-associated PCAs, cancer procoagulant (CP) and tissue factor (TF), inflammatory cell and vascular cell infiltration and fibrin deposition in human tumors. We will characterize the PCAs from homogeneous cell populations isolated from primary and metastatic tumors in these models, utilizing traditional biochemical methods and specific immunologic and functional probes. The long-term goals for this research are to: 1) provide a better understanding of the mechanism(s) for fibrin deposition in cancer; 2) develop strategies for the specific inhibition of cell mediated fibrin deposition; 3) demonstrate inhibition of metastasis formation by inhibiting cell-mediated clotting.
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