Expression of the vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasms

• Published in: The Journal of clinical investigation Vol. 91; no. 1; pp. 153 - 159
• Main Authors: BERKMAN, R. A, MERRILL, M. J, REINHOLD, W. C, MONACCI, W. T, SAXENA, A, CLARK, W. C, ROBERTSON, J. T, ALI, I. U, OLDFIELD, E. H
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 1993
• Subjects: Base Sequence; Biological and medical sciences; Blotting, Southern; Brain - metabolism; Brain - pathology; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain Neoplasms - secondary; Central Nervous System Neoplasms - genetics; Central Nervous System Neoplasms - metabolism; Central Nervous System Neoplasms - pathology; DNA, Neoplasm - analysis; DNA, Neoplasm - genetics; Endothelial Growth Factors - analysis; Endothelial Growth Factors - genetics; Epilepsy - genetics; Epilepsy - metabolism; Epilepsy - pathology; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - pathology; Hemangiosarcoma - genetics; Hemangiosarcoma - metabolism; Hemangiosarcoma - pathology; Humans; Lymphokines - analysis; Lymphokines - genetics; Medical sciences; Meningeal Neoplasms - genetics; Meningeal Neoplasms - metabolism; Meningeal Neoplasms - pathology; Meningioma - genetics; Meningioma - metabolism; Meningioma - pathology; Molecular Sequence Data; Neurology; Oligodeoxyribonucleotides; Oligonucleotide Probes; Restriction Mapping; RNA, Messenger - analysis; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tumors of the nervous system. Phacomatoses; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Human; Nervous system diseases; Pathophysiology; Blood vessel; Tumor; Permeability; Growth factor
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci116165

Expression of the vascular permeability factor/vascular endothelial 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, respectively. VEGPF mRNA levels in CNS tumors vs. normal brain were investigated by the RNase protection assay. Significant elevation of VEGPF 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 associated with significant neovascularity or cerebral edema (2/10 pituitary adenomas and 0/5 nonastrocytic gliomas) had significantly increased levels of VEGPF mRNA. The relative abundance of the forms of VEGPF mRNA was consistent in tumor and normal brain: VEGPF495 > VEGPF363 > VEGPF567. In situ hybridization confirmed the presence of VEGPF mRNA in tumor cells and its increased abundance in capillary hemangioblastomas. Our results suggest a significant role for VEGPF in the development of CNS tumor neovascularity and peritumoral edema.