The constitutive level of vascular endothelial growth factor (VEGF) is more important than hypoxia-induced VEGF up-regulation in the angiogenesis of human melanoma xenografts

Angiogenesis of tumours might develop as a result of environmental conditio ns, such as hypoxia, and/or as a result of genetic alterations specific for tumour cells. The relative contributions of these mechanisms were investig ated by comparing the in vivo expression of vascular endothelial growth fac tor (VEGF) and basic fibroblast growth factor (bFGF) to the hypoxic fractio n, the angiogenic potential and the vascular density of four human melanoma lines (A-07, D-12, R-18, U-25) grown intradermally in Balb/c nu/nu mice. V EGF expression, bFGF expression and expression of pimonidazole, a marker of hypoxic cells, were investigated by immunohistochemistry. An association b etween high VEGF and bFGF expression and high angiogenic potential was dete cted, suggesting an important role for VEGF/bFGF in the angiogenesis of mel anomas. High VEGF/bFGF expression was also related to tow hypoxic fraction and high vascular density. Thus, the constitutive, genetically determined l evel of VEGF was probably more important than hypoxia-induced upregulation in the angiogenesis of the melanoma xenografts. (C) 2000 Cancer Research Ca mpaign.