Direct FGF receptor 1 activation through an anti-idiotypic strategy mimicks the biological activity of FGF-2 and inhibits the progression of the bladder carcinoma derived from NBT-II cells.
Oncogene
; 23(40): 6769-78, 2004 Sep 02.
Article
em En
| MEDLINE
| ID: mdl-15273729
ABSTRACT
The hypothesis that tumor growth is angiogenesis-dependent has been documented by a considerable body of direct and indirect experimental data. Since the discovery of the vascular endothelial growth factor (VEGF), most attention has been focused on the VEGF system. Although fibroblast growth factors 1 and 2 (FGF-1 and FGF-2) can exert a strong angiogenic activity when they are supplied as a single pharmacological agent, their role in pathological angiogenesis in preclinical models remains controversial. To decipher the contribution of FGF receptors in various models of angiogenesis, we took advantage of the anti-idiotypic strategy to obtain circulating agonists specific for FGFR-1 and FGFR-2 (AIdF-1 and AIdF-2). They mimicked FGF-1 and FGF-2 for receptor binding, signal transduction, proliferation of endothelial cells and differentiation of the bladder carcinoma cell NBT-II which expresses FGFR-2b but not FGFR-1. The constitutive expression of FGFR-1 allowed binding of FGF-2 and AIdF-2 and inhibition of the proliferation of NBT-II cells. AIdF-1 and AIdF-2 induced angiogenesis in the corneal pocket assay. Although FGFR-1 dimerization achieved by AIdF-2 injection led to highly differentiated and smaller NBT-II tumors, no sign of reduction of tumor angiogenesis was observed, thus suggesting that endothelial cells are resistant to FGF.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Bexiga Urinária
/
Fator 2 de Crescimento de Fibroblastos
/
Receptores de Fatores de Crescimento de Fibroblastos
/
Receptores Proteína Tirosina Quinases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
França