No abstract

The (15)(16)(17). These factors include acidic fibroblast growth factor, basic fibroblast growth factor (bFGF), epidermal growth factor, transforming growth factors a and 13, tumor necrosis factor a, and vascular endothelial growth factor (VEGF). VEGF is secreted by a number of tumors and is normally expressed in the kidney, brain, and other tissues (18-22).VEGF is also markedly elevated in both VHL-associated and sporadic central nervous system hemangioblastomas (23, 24) and renal carcinomas (25,26). In addition to having mitogenic activity on endothelial cells, VEGF also induces vascular permeability, which may lead to extravasation of plasma proteins and deposition of fibrin, providing an extracellular support for tumor cell and endothelial cell growth.In the present study the effects of retroviral transduction of the VHL cDNA into renal carcinoma cell lines was evaluated. ITo whom reprint requests should be addressed

(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. (J. Clin. Invest. 1993. 91:153-159.)

Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is a approximately 43-kDa secreted protein that has been shown in bioassays to induce endothelial proliferation, angiogenesis, and capillary hyperpermeability. VPF has been suggested to play an important role in the physiology of normal vasculature. To further elucidate the natural functions of VPF in vivo, the expression of VPF in normal tissues was examined using Northern blot analysis and in situ hybridization histochemistry. VPF mRNA is expressed in the brain, kidney, liver, lung, and spleen of the healthy adult rat. On Northern blots, the relative abundance of VPF mRNA observed in these tissues was highest in the lung and lowest in the spleen. As determined by in situ hybridization, the patterns of VPF expression are organ specific. Hybridization of an antisense VPF probe was concentrated in the cerebellar granule cell layer of the brain and in the glomeruli and tubules of the kidney. In the liver and lung, intense hybridization was observed homogeneously throughout both tissues, demonstrating that VPF mRNA is present in virtually every hepatocyte and pulmonary alveolar cell. Hybridization to the spleen was weaker and more diffuse. The widespread expression and organ-specific distribution of VPF mRNA in normal rat tissues supports the suggestion of an extensive role for this factor in the physiology of normal vasculature.