Integrin beta4 signaling promotes tumor angiogenesis.
Cancer Cell
; 6(5): 471-83, 2004 Nov.
Article
em En
| MEDLINE
| ID: mdl-15542431
ABSTRACT
Mice carrying a targeted deletion of the signaling portion of the integrin beta4 subunit display drastically reduced angiogenesis in response to bFGF in the Matrigel plug assay and to hypoxia in the retinal neovascularization model. Molecular cytology indicates that alpha6beta4 signaling promotes branching of beta4+ medium- and small-size vessels into beta4- microvessels without exerting a direct effect on endothelial cell proliferation or survival. Signaling studies reveal that alpha6beta4 signaling induces endothelial cell migration and invasion by promoting nuclear translocation of P-ERK and NF-kappaB. Upon subcutaneous implantation of various cancer cells, the mutant mice develop smaller and significantly less vascularized tumors than wild-type controls. These results provide genetic evidence that alpha6beta4 signaling promotes the onset of the invasive phase of pathological angiogenesis and hence identify a novel target for antiangiogenic therapy.
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Deleção de Genes
/
Integrina beta4
/
Integrina alfa6beta4
/
Neoplasias
/
Neovascularização Patológica
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article