Signaling pathways governing tumor angiogenesis.
Angiogenesis is regulated by the highly coordinated function of various proteins with pro- and antiangiogenic functions. Proangiogenic factors include vascular endothelial growth factor (VEGF), fibroblast growth factor, platelet-derived growth factor, insulin-like growth factor, transforming growth factor, angiopoietins, and several chemokines; antiangiogenic factors include thrombospondin-1, angiostatin, and endostatin. Matrix metalloproteinases display a dual role in vascular development. Notch signaling affects remodeling of the primary vascular network of uniformly sized vessels into functionally and morphologically distinct arteries, veins, and capillaries. Tumors, described as 'wounds that never heal', lose the appropriate balance among these factors. Although VEGF-targeted therapies are showing promise, new angiogenesis targets are needed to make additional gains. Here, we highlight recent advances in our understanding of the regulation of tumor angiogenesis and discuss the potential of molecular targeting as a new therapeutic approach.
Department of Gastroenterology and Hepatology, Kinki University, Ohno-Higashi, Osakasayama, Japan.
Toshiharu
T
Sakurai
Masatoshi
M
Kudo
D020533:Angiogenesis Inhibitors / Q000378:metabolism / Q000627:therapeutic use; D042682:Angiopoietins / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D042764:Receptors, TIE / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D017154:Stromal Cells; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D042682:Angiopoietins; D002135:Calcium-Binding Proteins; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010982:Platelet-Derived Growth Factor; D000072099:Serrate-Jagged Proteins; D016212:Transforming Growth Factor beta; D042442:Vascular Endothelial Growth Factors; D005346:Fibroblast Growth Factors; D042764:Receptors, TIE; D048031:JNK Mitogen-Activated Protein Kinases; D020782:Matrix Metalloproteinases