Tumor angiogenesis and the role of vascular cell integrin alphavbeta3.
Angiogenesis is a critical process for the growth and metastatic properties of all solid tumors. Recent biological and molecular studies have begun to elucidate the basic mechanisms of vascular cell proliferation, motility, and differentiation in vitro and in vivo. With this knowledge, it should be feasible to devise therapeutic strategies to selectively target and perturb the biological processes of angiogenic vascular cells, thereby leading to effective inhibitors of angiogenesis. This strategy has led to the development of antagonists to integrin alpha v beta 3, which promote the unscheduled programmed cell death of newly sprouting blood vessels. These antagonists cause regression of preestablished human tumors growing in laboratory animals and thus may lead to an effective therapeutic approach for most solid tumors in humans. Studies are currently aimed at designing highly specific small organic integrin inhibitors that will disrupt the signals enabling vascular cells to respond to the tumor-associated extracellular environment and to promote tumor-induced angiogenesis.
Varner
J A
JA
Department of Immunology, Scripps Research Institute La Jolla, California, USA.
Cheresh
D A
DA
D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D002648:Child; D017322:Clinical Trials, Phase II as Topic; D016228:Endothelial Growth Factors / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000502:physiology; D005128:Eye Diseases / Q000503:physiopathology; D005260:Female; D005346:Fibroblast Growth Factors / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008222:Lymphokines / Q000502:physiology; D008297:Male; D008666:Metalloendopeptidases / Q000502:physiology; D009363:Neoplasm Proteins / Q000502:physiology*; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D009842:Oligopeptides / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology; D017978:Receptors, Growth Factor / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor; D019030:Receptors, Vitronectin / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D016228:Endothelial Growth Factors; D016326:Extracellular Matrix Proteins; D008222:Lymphokines; D009363:Neoplasm Proteins; D009842:Oligopeptides; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D019030:Receptors, Vitronectin; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005346:Fibroblast Growth Factors; C047981:arginyl-glycyl-aspartic acid; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D008666:Metalloendopeptidases