In human malignant glioma samples (39 glioblastomas, 21 anaplastic astrocytomas and 4 anaplastic oligoastrocytomas), protein expression of VEGF, and its specific natural inhibitor, sFlt1, as well as vessel architecture were assessed.
Our analysis suggests that many of the most statistically significant genes work together in a HIF1A/VEGF-regulated network to increase angiogenesis and invasion in GBM when compared to AA.
However, the tumors formed by the cells expressing exogenous VEGF (121) or VEGF (165) retained the phenotype of AA, lacking areas of necrosis that are the hallmark of the GBM phenotype.
In this study, pharmacologic inhibitors were used to specifically inhibit PI3-kinase and MEK1/2 activity in human malignant astrocytoma cell lines, and their effects on VEGF expression were determined.