Angiostatic activity of synthetic inhibitors of urokinase type plasminogenactivator

We hypothesize that tumor angiogenesis can be limited by the reduction of e nzymatic activity of the urokinase type plasminogen activator. The proposed mechanism is elimination of proteolytic activity by the advancing tip of c apillaries which utilize proteolysis to produce space needed for vessel exp ansion. To test our hypothesis, we have investigated the angiostatic activi ty of synthetic low molecular weight inhibitors of urokinase: amiloride, be nzamidine, EGCG, B428, and B623 using the chicken embryo corioallantoic mem brane (CAM) model. We found that all tested inhibitors of urokinase cause a significant reduction of angiogenesis.