Systemic activation of the vascular endothelial growth factor receptor KDR/flk-1 selectively triggers endothelial cells with an angiogenic phenotype.
The hypothesis that tumor growth is angiogenesis dependent has been documented by a considerable body of direct and indirect experimental data. A prerequisite for the development of novel anti-angiogenic agents is the design of drugs that would be active only on those endothelial cells with an angiogenic phenotype. We took advantage of the anti-idiotypic strategy to obtain circulating agonists specific for the vascular endothelial growth factor receptor KDR/flk-1 (J-IgG). They induced in the absence of VEGF cell proliferation in vitro and angiogenesis in the corneal pocket assay either through local or systemic delivery. Intraperitoneal injections of J-IgG in nude mice grafted with a prostatic adenocarcinoma led to tumor enlargement associated with an increase in both tumor vascularization and proliferation. In contrast KDR/flk-1 overstimulation had no detectable effect on normal tissues. These data underline that KDR/flk-1 is a functional marker of the angiogenic phenotype of endothelial cells.
Ortéga
N
N
Laboratoire de Biologie Moléculaire Eucaryote, Toulouse, France.
Jonca
F
F
Vincent
S
S
Favard
C
C
Ruchoux
M M
MM
Plouët
J
J
D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D007074:Immunoglobulin G / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D007130:Immunoglobulin Idiotypes / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D007267:Injections; D008024:Ligands; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000473:pathology; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000378:metabolism / Q000502:physiology*; D040262:Receptors, Vascular Endothelial Growth Factor; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D008024:Ligands; 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