Proteases are indispensable for tumor growth, angiogenesis, and metastasis. These proteases are produced by tumor cells, stromal cells, and by the host coagulation cascade. Protease-activated receptor-1 (PAR-1) and PAR-2 are G protein-coupled receptors that serve as the cellular receptors for several of these proteases, including activated coagulation factor VII (FVIIa), activated coagulation factor X (FXa), and thrombin. PAR-1 and PAR-2 have been found to be overexpressed in breast cancer and activation of these receptors contributes to the malignant phenotype of the cells. Activation of PAR-1 or PAR-2 by coagulation proteases increases the expression of urokinase plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1). uPA and PAI-1 are overexpressed in breast cancer patients and contribute to tumor angiogenesis, tumor growth, and metastasis. Using the highly metastatic 4T1 murine mammary adenocarcinoma model, I examined the effects of coagulati
