The goal of our research is to understand how angiogenesis, and receptor mediated growth mechanisms contribute to nervous system neoplasia. Human malignant gliomas are among the most malignant and most intensely vascularized solid tumors. Tumor angiogenesis is believed to be mediated by soluble factors released from tumor cells which then act on endothelial cells in a paracrine manner. . Vascular endothelial growth factor (VEGF) is a prime regulator of normal and tumor angiogenesis as well as vasculogenesis. VEGF is expressed in glioma cells and its receptors (FLT-1 and KDR) are expressed in the same gliomas. We used a synthetic tyrosine phosphopeptide to raise an antibody that reports the phosphorylation state of tyrosine in the KDR receptor. Immunoblotting and immunostaining of this antibody shows that the KDR receptor is activated in human high grade astrocytomas (71%), but not low grade astrocytomas (0%).
Angiostatin and endostatin are two endogenous inhibitors of tumor-related angiogenesis by selective inhibition of endothelial cell growth. We have demonstrate that systemic administration of angiostatin efficiently suppresses malignant glioma growth in vivo. We are presently examining the effects of endostatin on glioma growth. The findings of the current study strongly support the hypothesis that the onset of angiogenesis is an important event during the disease progression of gliomas.