Selective activity against proliferating tumor endothelial cells by CVX-22, a thrombospondin-1 mimetic CovX-Body.
Anticancer Res
; 29(6): 2243-52, 2009 Jun.
Article
em En
| MEDLINE
| ID: mdl-19528489
ABSTRACT
CVX-22 is a CovX-Body, produced by covalently attaching a thrombospondin-1 (TSP-1) type 1 repeat peptide mimetic to a humanized IgG1 molecule. To dissect the antiangiogenic mechanism of CVX-22, the numbers and proliferative status of defined tumor endothelial cell (TEC) subsets from the B16 and C32 melanoma models were examined. CVX-22 treatment reduced the numbers of activated, vascular endothelial growth factor receptor 2 (VEGFR2)-positive TECs. Because the vast majority of mitotically active TECs reside in the VEGFR2 subset, a reduction in numbers of this compartment resulted in an 82% overall decrease in BrdU labeling of TEC. However, the rate of proliferation and VEGFR2 receptor density of this VEGFR2-positive subpopulation were unaffected. Instead, CVX-22 induced endothelial cell apoptosis both in vitro and in vivo, indicating that CVX-22 acts by selective deletion of activated, VEGFR2-positive TEC. The overrepresentation of activated cells in sites of tumor angiogenesis may confer a unique specificity of CVX-22 for tumor vasculature.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Melanoma Experimental
/
Imunoglobulina G
/
Endotélio Vascular
/
Trombospondina 1
/
Proliferação de Células
/
Neovascularização Patológica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Anticancer Res
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos