Endothelial-Rac1 Is Not Required for Tumor Angiogenesis unless αvβ3-Integrin Is Absent

Endothelial cell migration is an essential aspect of tumor angiogenesis. Rac1 activity is needed for cell migration in vitro implying a requirement for this molecule in angiogenesis in vivo. However, a precise role for Rac1 in tumor angiogenesis has never been addressed. Here we show that depletion...

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Bibliographic Details
Published in:PloS one 2010-03, Vol.5 (3), p.e9766
Main Authors: D'Amico, Gabriela, Robinson, Stephen D., Germain, Mitchel, Reynolds, Louise E., Thomas, Gareth J., Elia, George, Saunders, Garry, Fruttiger, Marcus, Tybulewicz, Victor, Mavria, Georgia, Hodivala-Dilke, Kairbaan M.
Format: Article
Language:English
Subjects:
Angiogenesis
Biology
Cancer therapies
Cell Biology/Cell Adhesion
Cell Biology/Cell Signaling
Cell culture
Cell migration
Colorectal cancer
Dentistry
Endothelial cells
Laboratories
Ligands
Medical research
Medicine
Mice
Oncology
Phosphorylation
Rac1 protein
Transgenic animals
Tumors
Vascular endothelial growth factor
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Summary:Endothelial cell migration is an essential aspect of tumor angiogenesis. Rac1 activity is needed for cell migration in vitro implying a requirement for this molecule in angiogenesis in vivo. However, a precise role for Rac1 in tumor angiogenesis has never been addressed. Here we show that depletion of endothelial Rac1 expression in adult mice, unexpectedly, has no effect on tumor growth or tumor angiogenesis. In addition, repression of Rac1 expression does not inhibit VEGF-mediated angiogenesis in vivo or ex vivo, nor does it affect chemotactic migratory responses to VEGF in 3-dimensions. In contrast, the requirement for Rac1 in tumor growth and angiogenesis becomes important when endothelial β3-integrin levels are reduced or absent: the enhanced tumor growth, tumor angiogenesis and VEGF-mediated responses in β3-null mice are all Rac1-dependent. These data indicate that in the presence of αvβ3-integrin Rac1 is not required for tumor angiogenesis.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0009766