In embryoid bodies, embryonic stem cells can differentiate into a variety of cell lineages, including endothelial cells. In this model, both VEGF and FGF lead to improved angioblast survival but only VEGF supports the formation of primitive endothelial tubes. Also, in embryoid bodies in which VEGFVEGFR function is impaired, FGF stimulates the formation of endothelial cell clusters that fail to develop into primitive vessels.FGF is present in blood at concentrations equal to. pM under different pathological conditions whereas its binding partners are present at concentrations that are up to, times higher. ECM degradation can lead to mobilization of entrapped FGF with consequent activation of an angiogenic response. The ability of low molecular weight heparin fragments to reduce the angiogenic activity of FGF and VEGF support this hypothesis.For this reason it has been considered as a target for the development of anticancer therapies. Endothelial cell adhesion and activation by immobilized FGF may have relevance in vivo.Relevant to this point, heparinbound FGF retains it celladhesive capacity. Integrin avb is expressed also at the luminal aspect of endothelium suggesting that it may also mediate the biological affects exerted by free FGF.Actually, antiavb antibodies inhibit mitogenesis and protease upregulation triggered by free FGF in cultured endothelial cells.For instance, gangliosides are highly expressed in the hypervascularized areas of gliomas where they regulate angiogenesis. In the extracellular environment, gangliosides compete with free heparin for the binding to the growth factor.Ganglioside GM is expressed on the endothelial cell surface and binds FGF with an afnity that is signicantly higher than that of its free counterpart. Under these conditions, GM acts as a functional FGF coreceptor.TSP was the rst endogenous inhibitor of angiogenesis to be identied and its effect is due, at least in part, to its capacity to bind FGF. Accordingly, TSP inhibits the mitogenic and chemotactic activity of FGF in endothelial cells.TSP also prevents the accumulation of FGF in the ECM and favors the mobilization of matrixM.FGFBP can serve as an angiogenic switch for different tumor cell lines, including squamous cell carcinoma and colon cancer cells. Fibrin binds FGF, but not FGF, with high afnity without affecting FGFFGFR interaction.Indeed, FGF bound to immobilized brin supports endothelial cell proliferation. Both aM and aM bind a variety of cytokines and growth factors, including FGF, FGF, FGF, and FGF, but not FGF, FGF, FGF, and FGF. PTX is synthesized and released by activated mononuclear phagocytes and endothelial cells and acts as a soluble pattern recognition receptor with unique functions in SKI II various physiopathological conditions.These functions relay, at least in part, on the capacity of PTX to bind different structures. PTX binds FGF, but not FGF and FGF, with high afnity. Relevant to this point, FGF and PTX retains their binding capacity independently of their free or immobilized status. The heparinbinding CXC chemokine platelet factor. These data suggest that FGF production and release may occur in vivo and may inuence the growth and neovascularization of tumor Dypyridamole xenografts.Accordingly, targeting FGFBP with specic ribozymes inhibits the growth and vascularization of xenografted tumors in mice.