Effect of VEGF and VEGF Trap on vascular endothelial cell signaling in tumors
Open Access
- 15 December 2010
- journal article
- Published by Taylor & Francis Ltd in Cancer Biology & Therapy
- Vol. 10 (12), 1326-1333
- https://doi.org/10.4161/cbt.10.12.14009
Abstract
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 antagonistKeywords
This publication has 37 references indexed in Scilit:
- Tie2 in Tumor Endothelial Signaling and Survival: Implications for Antiangiogenic TherapyMolecular Cancer Research, 2009
- The VEGF pathway and the AKT/mTOR/p70S6K1 signalling pathway in human epithelial ovarian cancerBritish Journal of Cancer, 2009
- Vascular permeability, vascular hyperpermeability and angiogenesisAngiogenesis, 2008
- Paclitaxel plus Bevacizumab versus Paclitaxel Alone for Metastatic Breast CancerNew England Journal of Medicine, 2007
- Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trialThe Lancet, 2007
- Predicting benefit from anti-angiogenic agents in malignancyNature Reviews Cancer, 2006
- VEGF receptor signalling ? in control of vascular functionNature Reviews Molecular Cell Biology, 2006
- Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesisExperimental Cell Research, 2005
- The biology of VEGF and its receptorsNature Medicine, 2003
- Hypoxia — a key regulatory factor in tumour growthNature Reviews Cancer, 2002