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

D'Amico, G; Robinson, SD; Germain, M; Reynolds, LE; Thomas, GJ; Elia, G; Saunders, G; ... Hodivala-Dilke, KM; + view all (2010) Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent. PLOS One , 5 (3) , Article e9766. 10.1371/journal.pone.0009766. Green open access

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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 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.

Type: Article
Title: Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0009766
Publisher version: http://dx.doi.org/10.1371/journal.pone.0009766
Language: English
Additional information: © 2010 D'Amico et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was funded by Cancer Research UK, the Medical Research Council, Breast Cancer Campaign, The Association for International Cancer Research, and The Health Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: Animals, Cell Movement, Chemotaxis, Endothelial Cells, Endothelium, Endothelium, Vascular, Humans, Integrin alphaVbeta3, Mice, Mice, Inbred C57BL, Neovascularization, Pathologic, Neuropeptides, Retinal Vessels, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-2, rac GTP-Binding Proteins, rac1 GTP-Binding Protein, rho GTP-Binding Proteins
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/1361428
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