During angiogenesis, new blood vessels grow by sprouting from established blood vessels; this process is characterized by a cascade of events including enzymatic degradation of basement membrane and endothelial cell migration, proliferation, and tube formation. These tumorsecreted growth factors have both direct and indirect effects on glioma angiogenesis: they can directly stimulate endothelial cell proliferation, mediate the expression of key proteases on endothelial cells necessary for angiogenesis, and regulate the expression of VEGF and of each other.They can act in a paracrine fashion, in which ligand is produced by cells distinct from the cells expressing receptor, or they may act in an autocrine manner in which the same cell type expresses ligand and receptor.Additionally, a potential role for FGF in this process will also be discussed.Of the proteins in the FGF family, FGF and FGF have been studied in greatest depth.While the targets of these factors are many, each exerts its effects through one or more members of four wellcharacterized FGF receptor families: FGF receptor. Early in vitro studies demonstrated high levels of expression of FGF mRNA and protein in UMG glioma cell lines. FGF overexpression has been linked to increased endothelial activity, as well.Strong expression of FGF has been reported in the perivascular space of more malignant tumors as compared to normal brain. Peritumoral endothelial cell FGF immunoreactivity has also been shown to correlate with tumor grade; capillaries in glioblastoma and anaplastic astrocytoma are immunoreactive for FGF, in contrast to those of lowgrade astrocytomas. Higher levels of FGF receptors have also been demonstrated in gliomas; indeed, it has been suggested that glioma grade is marked by the differential expression of FGFR molecules, with the malignant progression from glial cell to glioblastoma accompanied by diminishing levels of FGFR and increasing levels of FGFR. These Eltrombopag results suggest that alterations in FGFR signal transduction pathways may play a critical role in the malignant progression of astrocytic tumors.While these changes have been reported in glioma cells, there is conicting evidence regarding the status of FGFR expression on intratumoral endothelial cells. It is thought that FGF and FGF may participate in angiogenesis in two primary ways: by modulating endothelial cell activity and by regulating VEGF expression in tumor cells.Both factors are wellestablished mitogens and chemoattractants for endothelial cells. In order to invade extracellular matrix to vascularize new tissues, endothelial cells must enhance their expression of molecules that activate key proteases such as plasmin. One of such molecules, urokinasetype plasminogen activator, acts to convert the inactive zymogen plasminogen to the active proteolytic enzyme plasmin. Hordenine Plasmin, in turn, is able to degrade multiple extracellular matrix components including bronectin and laminin, permitting endothelial cell migration into new tissue space and has also been shown to induce expression of the receptor for uPA, thus modulating endothelial cell migration in a feedforward fashion.Hence one way in which FGF may participate in angiogenesis is by mediating the proteolytic digestion of ECM by invading endothelial cells.Furthermore, FGF is chemotactic for endothelial cells and has been shown to induce capillary endothelial cells to migrate into threedimensional collagen matrices to form capillarylike tubes.