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...

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Autores principales: 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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Publicado: Public Library of Science (PLoS) 2010
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Acceso en línea:https://doaj.org/article/41b0c7cc9f614c6dbf5291476797a248
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spelling oai:doaj.org-article:41b0c7cc9f614c6dbf5291476797a2482021-11-25T06:25:18ZEndothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent.1932-620310.1371/journal.pone.0009766https://doaj.org/article/41b0c7cc9f614c6dbf5291476797a2482010-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20339539/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Endothelial 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.Gabriela D'AmicoStephen D RobinsonMitchel GermainLouise E ReynoldsGareth J ThomasGeorge EliaGarry SaundersMarcus FruttigerVictor TybulewiczGeorgia MavriaKairbaan M Hodivala-DilkePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 3, p e9766 (2010)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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
Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent.
description 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.
format article
author 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
author_facet 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
author_sort Gabriela D'Amico
title Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent.
title_short Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent.
title_full Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent.
title_fullStr Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent.
title_full_unstemmed Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent.
title_sort endothelial-rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent.
publisher Public Library of Science (PLoS)
publishDate 2010
url https://doaj.org/article/41b0c7cc9f614c6dbf5291476797a248
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