Expression of the Vascular Permeability Factor/Vascular Endothelial Growth Factor Gene in Central Nervous System Neoplasms

Expression of the vascular permeability factor / vascular endo-thelial growth factor (VEGPF) gene was investigated in human central nervous system (CNS) neoplasms and normal brain. Adsorption of capillary permeability activity from human glioblastoma multiforme (GBM) cell conditioned medium and GBM cyst fluids by anti-VEGPF antibodies demonstrated that VEGPF is secreted by GBM cells and is present in sufficient quantities in vivo to induce vascular permeability. Cloning and sequencing of polymerase chain reaction-amplified GBM and normal brain cDNA demonstrated three forms of the VEGPF coding region (567, 495, and 363 nucleotides), corresponding to mature polypeptides of 189, 165, and 121 amino acids, re-spectively. VEGPF mRNA levels in CNS tumors vs. normal brain were investigated by the RNase protection assay. Signifi-cant elevation ofVEGPF gene expression was observed in 81% (22/27) of the highly vascular and edema-associated CNS neoplasms (6 /8 GBM, 8/8 capillary hemangioblastomas, 6/7 meningiomas, and 2/4 cerebral metastases). In contrast, only 13 % (2/15) of those CNS tumors that are not commonly asso-ciated with significant neovascularity or cerebral edema (2/10 pituitary adenomas and 0/5 nonastrocytic gliomas) had signifi-cantly increased levels of VEGPF mRNA. The relative abun-dance of the forms ofVEGPF mRNA was consistent in tumor and normal brain: VEGPF495> VEGPF363> VEGPF567. In situ hybridization confirmed the presence ofVEGPF mRNA in tumor cells and its increased abundance in capillary heman-gioblastomas. Our results suggest a significant role for VEGPF in the development of CNS tumor neovascularity and peritu-moral edema. (J. Clin. Invest. 1993. 91:153-159.) Key words: angiogenesis * brain * cerebral edema- glioblastoma- heman-gioblastom