The cerebral edema associated with malignant brain tumors causes neurologic deficits and increased intracranial pressure, and contributes to the morbidity and mortality associated with the neoplasm. We have determined that the conditioned medium of glioblastoma-derived cell cultures contains a substance capable of increasing the vascular permeability in a bioassay which measures the induction of capillary permeability in normal skin. This substance has been identified as vascular permeability factor (VPF) and may be partially responsible for the cerebral edema associated with brain tumors. VPF is a 40 kDa cationic polypeptide with some homology to PDGF. In addition to increasing capillary permeability, VPF is also an angiogenic, endothelial cell mitogen. Evidence to date suggests that the mechanism of action of VPF involves binding to endothelial cells through a specific receptor on the cell surface and subsequent influx of Ca2+. Glucocorticoids are a useful tool in the clinical management of brain tumor-associated edema. Our studies indicate that glucocorticoids act both at the level of the regulation of expression of VPF in brain tumor cells and on the target endothelial cells. Through these studies we hope to gain further insight into the mechanism of action of VPF, the role of this factor in brain tumor-associated edema and angiogenesis, and the possibility of improved therapeutic intervention.
