Vascular endothelial growth factor (VEGF) mRNA expression in human tumor models of different histologies

Abstract

Background: Vascular endothelial growth factor (VEGF) is a polypeptide with specific effects on endothelial cell growth and blood vessel permeability. Recent studies demonstrated a key role for VEGF in tumor neovascularization, which is a prerequisite for tumor proliferation and metastasis Patients and methods: We studied the expression of VEGF mRNA in a panel of 65 different human tumor xeno-grafts of various histologies using Northern and slot blot analyses. Analysis of vessel density was performed morphologically and after immunohistochemical staining of endothelial cells Results: High expression levels were observed in 22/65 tumors. In melanoma, colorectal, gastric, breast and lung cancers only single tumors showed strong expression signals, whereas 7/10 renal cell carcinoma (RCC) xenografts demonstrated high levels of VEGF mRNA. Vessel density analysis revealed a clear correlation of VEGF mRNA expression with vascularization in RCC (p - 0.0048). Patient survival time was compared for tumors showing high versus low expression values. The overall 5-year survival rate was significantly lower for patients with high expression of VEGF mRNA (p - 0.0306) Conclusions: These data support the hypothesis that tumor cells of various histologies secrete VEGF, which acts as a paracrine factor to induce endothelial cell proliferation and vessel formation and mediates tumor progression