Endothelial-Rac1 Is Not Required for Tumor Angiogenesis unless αvβ3-Integrin Is Absent
Copyright policy )Endothelial-Rac1 Is Not Required for Tumor Angiogenesis unless αvβ3-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.
- University of Southampton United Kingdom
- Queen Mary University of London United Kingdom
- UNIVERSITY COLLEGE LONDON, Bartlett School of Planning United Kingdom
- Institute of Cancer Research United Kingdom
- National Institute for Medical Research Tanzania (United Republic of)
Vascular Endothelial Growth Factor A, rac1 GTP-Binding Protein, rho GTP-Binding Proteins, 570, GROWTH-FACTOR, PATHOLOGICAL ANGIOGENESIS, General Science & Technology, Science, 610, Inbred C57BL, RAC1 ACTIVATION, Mice, Cell Movement, Vascular, MD Multidisciplinary, Animals, Humans, Endothelium, Neovascularization, Pathologic, Science & Technology, Neovascularization, Pathologic, Chemotaxis, Q, Neuropeptides, R, Endothelial Cells, Retinal Vessels, CAPILLARY LUMEN FORMATION, Integrin alphaVbeta3, CILENGITIDE EMD-121974, Vascular Endothelial Growth Factor Receptor-2, rac GTP-Binding Proteins, Multidisciplinary Sciences, 3-DIMENSIONAL EXTRACELLULAR MATRICES, Mice, Inbred C57BL, ADVANCED SOLID TUMORS, CRE-RECOMBINASE, Science & Technology - Other Topics, Medicine, Endothelium, Vascular, INTEGRIN INHIBITORS, VASCULAR DEVELOPMENT, Research Article
Vascular Endothelial Growth Factor A, rac1 GTP-Binding Protein, rho GTP-Binding Proteins, 570, GROWTH-FACTOR, PATHOLOGICAL ANGIOGENESIS, General Science & Technology, Science, 610, Inbred C57BL, RAC1 ACTIVATION, Mice, Cell Movement, Vascular, MD Multidisciplinary, Animals, Humans, Endothelium, Neovascularization, Pathologic, Science & Technology, Neovascularization, Pathologic, Chemotaxis, Q, Neuropeptides, R, Endothelial Cells, Retinal Vessels, CAPILLARY LUMEN FORMATION, Integrin alphaVbeta3, CILENGITIDE EMD-121974, Vascular Endothelial Growth Factor Receptor-2, rac GTP-Binding Proteins, Multidisciplinary Sciences, 3-DIMENSIONAL EXTRACELLULAR MATRICES, Mice, Inbred C57BL, ADVANCED SOLID TUMORS, CRE-RECOMBINASE, Science & Technology - Other Topics, Medicine, Endothelium, Vascular, INTEGRIN INHIBITORS, VASCULAR DEVELOPMENT, Research Article
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