Endothelial-Rac1 is not required for tumor angiogenesis unless αvβ3-integrin is absent

Gabriela D'Amico, Stephen D. Robinson, Mitchel Germain, Louise E. Reynolds, Gareth J. Thomas, George Elia, Garry Saunders, Marcus Fruttiger, Victor Tybulewicz, Georgia Mavria, Kairbaan M. Hodivala-Dilke

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Abstract

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 ß3-integrin levels are reduced or absent: the enhanced tumor growth, tumor angiogenesis and VEGF-mediated responses in ß3-null mice are all Rac1-dependent. These data indicate that in the presence of avß3-integrin Rac1 is not required for tumor angiogenesis.
Original languageEnglish
Article numbere9766
JournalPLoS One
Volume5
Issue number3
DOIs
Publication statusPublished - 22 Mar 2010

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