Elevated Flk1 (Vascular Endothelial Growth Factor Receptor 2) Signaling Mediates Enhanced Angiogenesis in beta3-Integrin-Deficient Mice Export

@article{citeulike:2742071, abstract = {Tumor growth, tumor angiogenesis, and vascular endothelial growth factor (VEGF)-specific angiogenesis are all enhanced in {beta}3-integrin-null mice. Furthermore, endothelial cells isolated from {beta}3-null mice show elevated levels of Flk1 (VEGF receptor 2) expression, suggesting that {beta}3-integrin can control the amplitude of VEGF responses by controlling Flk1 levels or activity. We now show that Flk1 signaling is required for the enhanced tumor growth and angiogenesis seen in {beta}3-null mice. Moreover, {beta}3-null endothelial cells exhibit enhanced migration and proliferation in response to VEGF in vitro, and this phenotype requires Flk1 signaling. Upon VEGF stimulation, {beta}3-null endothelial cells exhibit higher levels of phosphorylated Flk1 and extracellular-related kinases 1 and 2 than wild-type endothelial cells. Furthermore, signaling via ERK1/2 is required to mediate the elevated responses to VEGF observed in {beta}3-null endothelial cells and aortic rings in vitro. These data confirm that VEGF signaling via Flk1 is enhanced in {beta}3-integrin-deficient mice and suggests that this increase may mediate the enhanced angiogenesis and tumor growth observed in these mice in vivo. 10.1158/0008-5472.CAN-04-2760}, author = {Reynolds, Andrew R. and Reynolds, Louise E. and Nagel, Tobi E. and Lively, Julie C. and Robinson, Stephen D. and Hicklin, Daniel J. and Bodary, Sarah C. and Hodivala-Dilke, Kairbaan M.}, citeulike-article-id = {2742071}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/0008-5472.CAN-04-2760}, citeulike-linkout-1 = {http://cancerres.aacrjournals.org/cgi/content/abstract/64/23/8643}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/15574772}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=15574772}, day = {1}, doi = {10.1158/0008-5472.CAN-04-2760}, journal = {Cancer Res}, keywords = {angiogenesis, aorta, beta3\_integrin, endothelial\_cell, flk1, vegf}, month = {December}, number = {23}, pages = {8643--8650}, posted-at = {2008-05-01 09:26:00}, priority = {2}, title = {Elevated Flk1 (Vascular Endothelial Growth Factor Receptor 2) Signaling Mediates Enhanced Angiogenesis in {beta}3-Integrin-Deficient Mice}, url = {http://dx.doi.org/10.1158/0008-5472.CAN-04-2760}, volume = {64}, year = {2004} }

TY - JOUR ID - citeulike:2742071 L3 - citeulike-article-id:2742071 N2 - Tumor growth, tumor angiogenesis, and vascular endothelial growth factor (VEGF)-specific angiogenesis are all enhanced in {beta}3-integrin-null mice. Furthermore, endothelial cells isolated from {beta}3-null mice show elevated levels of Flk1 (VEGF receptor 2) expression, suggesting that {beta}3-integrin can control the amplitude of VEGF responses by controlling Flk1 levels or activity. We now show that Flk1 signaling is required for the enhanced tumor growth and angiogenesis seen in {beta}3-null mice. Moreover, {beta}3-null endothelial cells exhibit enhanced migration and proliferation in response to VEGF in vitro, and this phenotype requires Flk1 signaling. Upon VEGF stimulation, {beta}3-null endothelial cells exhibit higher levels of phosphorylated Flk1 and extracellular-related kinases 1 and 2 than wild-type endothelial cells. Furthermore, signaling via ERK1/2 is required to mediate the elevated responses to VEGF observed in {beta}3-null endothelial cells and aortic rings in vitro. These data confirm that VEGF signaling via Flk1 is enhanced in {beta}3-integrin-deficient mice and suggests that this increase may mediate the enhanced angiogenesis and tumor growth observed in these mice in vivo. 10.1158/0008-5472.CAN-04-2760 IS - 23 JF - Cancer Res EP - 8650 TI - Elevated Flk1 (Vascular Endothelial Growth Factor Receptor 2) Signaling Mediates Enhanced Angiogenesis in {beta}3-Integrin-Deficient Mice VL - 64 SP - 8643 KW - angiogenesis KW - aorta KW - beta3_integrin KW - endothelial_cell KW - flk1 KW - vegf AU - Reynolds, Andrew AU - Reynolds, Louise AU - Nagel, Tobi AU - Lively, Julie AU - Robinson, Stephen AU - Hicklin, Daniel AU - Bodary, Sarah AU - Hodivala-Dilke, Kairbaan PY - 2004/12/01/ UR - http://dx.doi.org/10.1158/0008-5472.CAN-04-2760 ER -