VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF) MESSENGER-RNA EXPRESSION INHUMAN TUMOR-MODELS OF DIFFERENT HISTOLOGIES

Background: Vascular endothelial growth factor (VEGF) is a polypeptide with specific effects on endothelial cell growth and blood vessel per meability. Recent studies demonstrated a key role for VEGF in tumor ne ovascularization, which is a prerequisite for tumor proliferation and metastasis. Materials and methods: We studied the expression of VEGF m RNA in a panel of 65 different human tumor xenografts of various histo logies using Northern and slot blot analyses. Analysis of vessel densi ty was performed morphologically and after immunohistochemical stainin g of endothelial cells. Results: High expression levels were observed in 22/65 tumors. In melanoma, colorectal, gastric, breast and lung can cers only single tumors showed strong expression signals, whereas 7/10 renal cell carcinoma (RCC) xenografts demonstrated high levels of VEG F mRNA. Vessel density analysis revealed a clear correlation of VEGF m RNA expression with vascularization in RCC (p = 0.0048). Patient survi val time was compared for tumors showing high versus low expression va lues. The overall 5-year survival rate was significantly lower for pat ients with high expression of VEGF mRNA (p = 0.0306). Conclusions: The se 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 .