How is angiogenesis regulated?

Angiogenesis is regulated by activator and inhibitor molecules. There are over a dozen different proteins which have been identified as angiogenic inhibitors and activators. The level of expression of angiogenic factors influence the activity/behavior of tumor cells. MMRN2 and FKBPL are examples of angiogenic inhibitors which act on specific cell surface receptors, and modulate pro-angiogenic function. Thrombospondin was the first identified endogenous angiogenic inhibitor. The goal of angiogenesis inhibitors is to block the growth of blood vessels which promote tumor growth rather than blocking the growth of tumor cells themselves.  Angiogenesis activators are tumor-secreted angiogenic growth factors that interact with their surface receptors expressed on endothelial cells. The most common angiogenic growth factors include VEGF, and bFGF. Once they come into contact with endothelial cells, they bind to the tyrosine kinase receptors on their membranes. More specifically, binding leads to dimerization of the receptors and activation of autophosphorylation of tyrosines on the receptor surface. This then initiates signaling proteins (e.g. PI3-kinase, Src) activators of transcriptions (which contain src-homology 2) domains, and signal transducers. Binding of the src-homology 2 regions of these proteins to the phosphotyrosines on receptor tyrosine kinases activates multiple pathways that are significant for triggering the process of the cell cycle.