The present study identifies the proteolytic cleavage of extracellular TFPI-2 by trypsinogen 4 as a new pathway regulating the response of tumor endothelial cell to the factors VEGF-A,FGF-2 and EGF (which characterize the angiogenic milieu), and hence tumor angiogenesis (Figure 6). The gene discussed is PRSS3; the disease is neoplasm.