title: VEGF-VEGF receptor complexes as markers of tumor vascular endothelium.
abstract: Vascular endothelial growth factor (VEGF) is a primary stimulant of the vascularization of solid tumors and has therefore been the focus of intense research aimed at blocking its activity in solid tumors. VEGF production by tumor cells is induced by oncogenic gene mutations and hypoxic conditions inside the tumor mass. VEGF receptor expression on endothelial cells lining blood vessels in the tumor is also induced by hypoxia and the increased local concentration of VEGF. Therefore in the tumor microenvironment there is an upregulation of both VEGF and its receptor leading to a high concentration of occupied receptor on tumor vascular endothelium. The VEGF-VEGF receptor complex (VEGF-VEGFR) presents an attractive target for the specific delivery of drugs or other effectors to tumor endothelium. Herein we review the development of monoclonal antibodies that selectively bind to the VEGF-VEGFR and their use as targeting agents that selectively bind to VEGF activated blood vessels. Additionally, we summarize the properties of 2C3, a novel monoclonal anti-VEGF antibody that blocks VEGF from binding to VEGFR2 but not VEGFR1. 2C3 may be utilized as both an anti-angiogenic agent by inhibiting VEGFR2 activity and potentially as a vascular targeting agent by binding to blood vessels that express the VEGF-VEGFR1 complex.
authors.affiliation: The Hope Heart Institute, Department of Vascular Biology, 1124 Columbia St., Seattle, WA 98104-2046, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Brekken
authors.forename: P E
authors.initials: PE
authors.lastname: Thorpe
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors / Q000276:immunology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D008222:Lymphokines / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000276:immunology / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor; D012039:Regional Blood Flow; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors; D008222:Lymphokines; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor