Endothelial-Rac1 Is Not Required for Tumor Angiogenesis unless alpha v beta 3-Integrin Is Absent
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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 beta 3-integrin levels are reduced or absent: the enhanced tumor growth, tumor angiogenesis and VEGF-mediated responses in beta 3-null mice are all Rac1-dependent. These data indicate that in the presence of alpha v beta 3-integrin Rac1 is not required for tumor angiogenesis.
3-DIMENSIONAL EXTRACELLULAR MATRICES; CAPILLARY LUMEN FORMATION; ADVANCED SOLID TUMORS; GROWTH-FACTOR; PATHOLOGICAL ANGIOGENESIS; CILENGITIDE EMD-121974; VASCULAR DEVELOPMENT; INTEGRIN INHIBITORS; RAC1 ACTIVATION; CRE-RECOMBINASE
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PLOS ONE, 2010, 5 (3)
PUBLIC LIBRARY SCIENCE