Growth factors in glioma angiogenesis: FGFs, PDGF, EGF, and TGFs

It has become well accepted that solid tumors must create a vascular system for nutrient delivery and waste removal in order to grow appreciably. This process, angiogenesis, is critical to the progression of gliomas, with vascular changes accompanying the advancement of these tumors. The cascade of events in this process of blood vessel formation involves a complex interplay between tumor cells, endothelial cells, and their surrounding basement membranes in which enzymatic degradation of surrounding ground substance and subsequent endothelial cell migration, proliferation, and tube formation occurs. It is likely that a host of growth factors is responsible for mediating these key events. To date, a role for Vascular Endothelial Growth Factor (VEGF) in glioma angiogenesis has been convincingly demonstrated. This review explores the contribution of other growth factors--Fibroblast Growth Factors (FGFs), Platelet-Derived Growth Factor (PDGF), Epidermal Growth Factor (EGF), and Transforming Growth Factors (TGFs)--to glioma angiogenesis. These growth factors may influence glioma angiogenesis by directly stimulating endothelial cell proliferation, by mediating the expression of key proteases on endothelial cells necessary for angiogenesis, or by regulating the expression of VEGF and of each other.