A peptide derived from TIMP-3 inhibits multiple angiogenic growth factor receptors and tumour growth and inflammatory arthritis in mice.
Angiogenesis
; 17(1): 207-19, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24129822
ABSTRACT
The binding of vascular endothelial growth factor (VEGF) to VEGF receptor-2 (VEGFR-2) on the surface of vascular endothelial cells stimulates many steps in the angiogenic pathway. Inhibition of this interaction is proving of value in moderating the neovascularization accompanying age-related macular degeneration and in the treatment of cancer. Tissue inhibitor of metalloproteinases-3 (TIMP-3) has been shown to be a natural VEGFR-2 specific antagonist-an activity that is independent of its ability to inhibit metalloproteinases. In this investigation we localize this activity to the C-terminal domain of the TIMP-3 molecule and characterize a short peptide, corresponding to part of this domain, that not only inhibits all three VEGF-family receptors, but also fibroblast growth factor and platelet-derived growth factor receptors. This multiple-receptor inhibition may explain why the peptide was also seen to be a powerful inhibitor of tumour growth and also a partial inhibitor of arthritic joint inflammation in vivo.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Artrite
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Inibidor Tecidual de Metaloproteinase-3
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Receptor 2 de Fatores de Crescimento do Endotélio Vascular
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Neoplasias Mamárias Experimentais
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Angiogenesis
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Reino Unido