Integrin beta4 signaling promotes tumor angiogenesis

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 br...

Full description

Saved in:
Bibliographic Details
Published in:Cancer cell 2004-11, Vol.6 (5), p.471-483
Main Authors: Nikolopoulos, Sotiris N, Blaikie, Pamela, Yoshioka, Toshiaki, Guo, Wenjun, Giancotti, Filippo G
Format: Article
Language:English
Subjects:
Animals
Cell Movement
Cell Proliferation
Cell Survival
Collagen
Drug Combinations
Endothelial Cells - pathology
Gene Deletion
Humans
Integrin alpha6beta4 - physiology
Integrin beta4 - genetics
Laminin
Mice
Mice, Mutant Strains
Models, Biological
Neoplasms - blood supply
Neovascularization, Pathologic - genetics
Paraffin Embedding
Proteoglycans
Retina
Signal Transduction - physiology
Tumor Cells, Cultured
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1535-6108