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Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent

Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent
Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-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 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 beta3-integrin levels are reduced or absent: the enhanced tumor growth, tumor angiogenesis and VEGF-mediated responses in beta3-null mice are all Rac1-dependent. These data indicate that in the presence of alphavbeta3-integrin Rac1 is not required for tumor angiogenesis.
1932-6203
e9776-[17pp]
Thomas, G.J.
2ff54aa9-a766-416b-91ee-cf1c5be74106
Thomas, G.J.
2ff54aa9-a766-416b-91ee-cf1c5be74106

Thomas, G.J. (2010) Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent. PLoS ONE, 5 (3), e9776-[17pp]. (doi:10.1371/journal.pone.0009766). (PMID:20339539)

Record type: Article

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 beta3-integrin levels are reduced or absent: the enhanced tumor growth, tumor angiogenesis and VEGF-mediated responses in beta3-null mice are all Rac1-dependent. These data indicate that in the presence of alphavbeta3-integrin Rac1 is not required for tumor angiogenesis.

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Published date: March 2010

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Local EPrints ID: 179137
URI: http://eprints.soton.ac.uk/id/eprint/179137
ISSN: 1932-6203
PURE UUID: 167dd88e-dcf0-457c-b447-22580f9611dc

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Date deposited: 08 Apr 2011 09:21
Last modified: 14 Mar 2024 02:47

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