Regulation of angiogenesis by SPARC and angiostatin: implications for tumor cell biology.

The formation of blood vessels through endothelial cell proliferation from extant vasculature (angiogenesis) is a prerequisite for the remodeling, regeneration and repair of tissue. In pathological processes, angiogenesis is a major limiting step in tumor growth and is necessary for tumor formation at metastatic sites. Angiogenesis consists of a sequence of events that include (i) dissolution of the basement membrane, (ii) migration and (iii) proliferation of endothelial cells, (iv) formation of the vascular loop, and (v) formation of a new basement membrane. A variety of factors control and regulate these multiple steps during which the endothelium gives rise to new vessels. Growth factors such as vascular endothelial growth factor or platelet-derived growth factor act directly on endothelial cells and/or activate inflammatory cells (monocytes and T lymphocytes) which in turn synthesize angiogenic factors. SPARC (Secreted Protein Acidic and Rich in Cytsteine), in conjunction with other known angiogenic factors, might act pleiotropically during angiogenesis. Recently, angiostatin, a novel endogenous inhibitor of metastasis, has been reported. This protein, a cleavage product of plasminogen, most likely acts through inhibition of angiogenesis. Current research is focused on the angiogenic and antiangiogenic properties of SPARC and angiostatin and will provide us with a better understanding of how these important factors regulate angiogenesis.