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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Effect of VEGF and VEGF Trap on vascular endothelial cell signaling in tumors
Cancer Biology and Therapy, Volume 10, No. 12, Year 2010
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Description
Vascular endothelial growth factor (VEGF) A is a major promoter of tumor angiogenesis and a prime target of antiangiogenic cancer therapy. To examine whether endothelial cell signaling might provide histological biomarkers of angiogenesis and VEGF activity in vivo, normal mouse organs and multiple tumor models were studied immunohistochemically for endothelial expression of activated ERK, STAT3 and AKT. Phospho(p)-ERK and p-STAT3 expression was negligible in the endothelia of normal organs but was significantly elevated in tumor endothelium. p-AKT was present at significant and comparable levels in both tumor and normal endothelia. In K1735 tumors induced to express more VEGF, endothelial p-ERK, p-STAT3 and p-AKT increased accompanied by signs of accelerated angiogenesis. Treatment of K1735 and Colo- 205 tumors with the VEGF inhibitor, VEGF Trap (aflibercept), decreased tumor endothelial p-ERK, p-STAT3 and p-AKT expression accompanied by signs of antiangiogenic effect. These results show that endothelial p-ERK and p-STAT3 (but not p-AKT) distinguish tumor from normal vessels and that the presence of these two signaling intermediates may be useful indicators of tumor angiogenic activity and angiogenesis inhibition by VEGF antagonists. © 2010 Landes Bioscience.
Authors & Co-Authors
Lassoued, Wiem
United States, Philadelphia
Penn Medicine
Tunisia, Tunis
University of Carthage
Murphy, Danielle
United States, Philadelphia
Penn Medicine
Tsai, Jeff
United States, Philadelphia
Penn Medicine
Oueslati, Ridha
Tunisia, Tunis
University of Carthage
Thurston, Gavin
United States, Tarrytown
Regeneron Pharmaceuticals, Inc.
Lee, William M.F.
United States, Philadelphia
Penn Medicine
Statistics
Citations: 38
Authors: 6
Affiliations: 3
Identifiers
Doi:
10.4161/cbt.10.12.14009
ISSN:
15384047
e-ISSN:
15558576
Research Areas
Cancer