Solorzano CC, Jung YD, Bucana CD, McConkey DJ, Gallick GE, McMahon G, Ellis LM
Cancer Res. 2001 61 (19)
Alterations in endothelial cell (EC) signaling could serve as a marker of effective antiangiogenic therapy. We determined the effect of an antiangiogenic tyrosine kinase inhibitor, SU6668, on tumor EC signaling in liver metastases in mice. In vitro immunofluorescence verified that pretreatment of ECs with SU6668 before exposure to VEGF decreased in vitro phosphorylation of Erk and Akt. Using double-fluorescence immunohistochemistry, phosphorylated Erk and Akt were constitutively expressed in ECs in liver metastases in untreated mice, but SU6668 blocked activation of these signaling intermediates. Determining the activation status of the Erk and Akt signaling pathways in tumor ECs may serve as a surrogate marker for the effectiveness of antiangiogenic regimens.
MeSH Terms (30)Androstadienes Angiogenesis Inhibitors Biomarkers, Tumor Blotting, Western Endothelial Growth Factors Endothelium, Vascular Enzyme Activation Enzyme Inhibitors Flavonoids Fluorescent Antibody Technique Humans Indoles Liver Neoplasms Lymphokines MAP Kinase Signaling System Mitogen-Activated Protein Kinase Kinases Neovascularization, Pathologic Phosphatidylinositol 3-Kinases Phosphoinositide-3 Kinase Inhibitors Phosphorylation Protein-Serine-Threonine Kinases Proto-Oncogene Proteins Proto-Oncogene Proteins c-akt Pyrroles Receptor Protein-Tyrosine Kinases Receptors, Growth Factor Receptors, Vascular Endothelial Growth Factor Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Wortmannin