title: Antiangiogenic approaches to renal cell carcinoma : assays for inhibitors and clinical trials.
abstract: Angiogenesis-the formation of new blood vessels from preexisting ones-is a complex process regulated by a number of soluble factors as well as important interactions between endothelial cells, extracellular matrix components, and adjacent cells (1-5). Activation of the endothelial cell, which occurs when the balance between proangiogenic and antiangiogenic signals within a given microenvironment tilts in a positive direction, leads initially to increased expression of proteases, allowing the endothelial cell to mobilize itself and release inducers sequestered within the matrix (1,6,7). This is followed by endothelial-cell proliferation and migration and culminates in reorganization of the endothelial cell plexus to form tubules and eventually capillary structures that can conduct blood. Most proangiogenic factors-such as VEGF and basic fibroblast growth factor (bFGF)-are peptide growth factors that bind to transmembrane-receptor tyrosine kinases on the surface of the endothelial cell, initiating intracellular transduction pathways resulting in cellular activation (8,9). Other important angiogenic factors-the angiopoietins-further modulate this process by stabilizing or destabilizing interactions between small blood vessels and adjacent pericytes (10 ). Expression of angiopoietin 2 results in dissociation of pericytes, which can lead to endothelial-cell activation or vascular regression, depending on whether angioinductive or angioinhibitory signals predominate (10,11). In contrast, angiopoietin 1 stabilizes interactions with pericytes and promotes vascular quiescence (10,12).
authors.affiliation: Department of Urology and the R. H. Lurie Cancer Center, Northwestern University School of Medicine, Chicago, IL.
authors.forename: S C
authors.initials: SC
authors.lastname: Campbell
authors.forename: F K
authors.initials: FK
authors.lastname: Reiher
authors.forename: N D
authors.initials: ND
authors.lastname: Smith