Systemic activation of the vascular endothelial growth factor receptor KDR/flk-1 selectively triggers endothelial cells with an angiogenic phenotype.
Am J Pathol
; 151(5): 1215-24, 1997 Nov.
Article
in En
| MEDLINE
| ID: mdl-9358746
ABSTRACT
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.
Full text:
1
Database:
MEDLINE
Main subject:
Endothelium, Vascular
/
Receptors, Growth Factor
/
Receptor Protein-Tyrosine Kinases
/
Neovascularization, Physiologic
Limits:
Animals
Language:
En
Journal:
Am J Pathol
Year:
1997
Type:
Article
Affiliation country:
France