The article reviews the role of the fibroblast growth factor (FGF) system in angiogenesis, particularly in tumor vascularization. FGFs are a family of heparin-binding growth factors that exert their pro-angiogenic activity by interacting with various endothelial cell surface receptors, including tyrosine kinase receptors, heparan-sulfate proteoglycans, and integrins. The activity of FGFs is modulated by a variety of free and extracellular matrix-associated molecules, and they can interact with vascular endothelial growth factors (VEGFs) and inflammatory cytokines/chemokines, influencing blood vessel growth in pathological conditions, including cancer. The review highlights the relevance of the FGF/FGF receptor system in adult angiogenesis and its contribution to tumor vascularization. Key points include: 1. **Pro-angiogenic Activity of FGFs**: FGFs induce endothelial cell proliferation, extracellular matrix degradation, migration, and morphogenesis through various signaling pathways. FGFs can act autocrinely, intracrinely, or paracrinely, and their effects are influenced by binding partners such as heparan-sulfate proteoglycans (HSPGs) and integrins. 2. **In Vivo Effects and Experimental Assays**: FGFs have been shown to promote angiogenesis in various experimental models, including the chick embryo chorioallantoic membrane (CAM) assay and rabbit cornea assays. The role of endogenous FGFs in angiogenesis remains less clear, but they can influence vascularization under certain conditions. 3. **Cross-talk with VEGF**: FGF2 and VEGF interact closely during angiogenesis, lymphangiogenesis, and vasculogenesis. FGF2 can indirectly promote angiogenesis by activating the VEGF/VEGFR system, and VEGF may require FGF2 for its angiogenic potential under specific conditions. 4. **FGF Interaction with Endothelial Cell Surface, Extracellular Matrix, and Free Molecules**: FGFs interact with various binding partners, including HSPGs, integrins, gangliosides, thrombospondin-1, and serum components like soluble FGFR1 and fibrinogen. These interactions modulate FGF activity and endothelial cell responses. 5. **FGF/FGFR System in Tumor Angiogenesis**: FGF2 is expressed in various tumor cell lines and can influence tumor growth and angiogenesis. In vivo studies show that FGF2 levels do not consistently correlate with microvessel density (MVD) in cancer patients, unlike VEGF. However, FGF2 can contribute to cancer progression by acting directly on tumor cells and influencing both vasculature and tumor parenchyma. Overall, the FGF/FGF receptor system plays a significant role in angiogenesis and tumor vascularization, and targeting this system may be a promising strategy for antiThe article reviews the role of the fibroblast growth factor (FGF) system in angiogenesis, particularly in tumor vascularization. FGFs are a family of heparin-binding growth factors that exert their pro-angiogenic activity by interacting with various endothelial cell surface receptors, including tyrosine kinase receptors, heparan-sulfate proteoglycans, and integrins. The activity of FGFs is modulated by a variety of free and extracellular matrix-associated molecules, and they can interact with vascular endothelial growth factors (VEGFs) and inflammatory cytokines/chemokines, influencing blood vessel growth in pathological conditions, including cancer. The review highlights the relevance of the FGF/FGF receptor system in adult angiogenesis and its contribution to tumor vascularization. Key points include: 1. **Pro-angiogenic Activity of FGFs**: FGFs induce endothelial cell proliferation, extracellular matrix degradation, migration, and morphogenesis through various signaling pathways. FGFs can act autocrinely, intracrinely, or paracrinely, and their effects are influenced by binding partners such as heparan-sulfate proteoglycans (HSPGs) and integrins. 2. **In Vivo Effects and Experimental Assays**: FGFs have been shown to promote angiogenesis in various experimental models, including the chick embryo chorioallantoic membrane (CAM) assay and rabbit cornea assays. The role of endogenous FGFs in angiogenesis remains less clear, but they can influence vascularization under certain conditions. 3. **Cross-talk with VEGF**: FGF2 and VEGF interact closely during angiogenesis, lymphangiogenesis, and vasculogenesis. FGF2 can indirectly promote angiogenesis by activating the VEGF/VEGFR system, and VEGF may require FGF2 for its angiogenic potential under specific conditions. 4. **FGF Interaction with Endothelial Cell Surface, Extracellular Matrix, and Free Molecules**: FGFs interact with various binding partners, including HSPGs, integrins, gangliosides, thrombospondin-1, and serum components like soluble FGFR1 and fibrinogen. These interactions modulate FGF activity and endothelial cell responses. 5. **FGF/FGFR System in Tumor Angiogenesis**: FGF2 is expressed in various tumor cell lines and can influence tumor growth and angiogenesis. In vivo studies show that FGF2 levels do not consistently correlate with microvessel density (MVD) in cancer patients, unlike VEGF. However, FGF2 can contribute to cancer progression by acting directly on tumor cells and influencing both vasculature and tumor parenchyma. Overall, the FGF/FGF receptor system plays a significant role in angiogenesis and tumor vascularization, and targeting this system may be a promising strategy for anti