VASCULAR-PERMEABILITY FACTOR EXPRESSION INFLUENCES TUMOR ANGIOGENESISIN HUMAN-MELANOMA LINES XENOGRAFTED TO NUDE-MICE

We studied the expression of the angiogenic factor vascular permeabili ty factor) (VPF, also called vascular endothelial growth factor), in h uman melanoma cells in vitro and in viva Melanoma lines that develop t umors with a low metastatic potential in nude mice were found to have low expression levels of VFP in vitro, and the VPF expression levels i n melanoma lines that yield highly metastatic xenografts were high. Ho wever, in vivo the correlation between VPF mRNA levels and the frequen cy of metastasis was lost; in all xenografts equally high levels of VP I; mRNA were found, independent of the parental cell line. Hence, in v ivo VPF gene expression was upregulated in the low expressing lilies. The external factor responsible for this induction may be hypoxia, giv en that we found that low oxygen tension caused a (reversible) increas e in the VPF mRNA levels in otherwise low expressing melanoma lines in vitro A melanoma line with an inducible VPF expression was engineered into a line with a constitutive VPF expression. In the xenografts fro m this line a change in the vascular architecture teas seen, indicatin g that the pattern or the level of VPF expression is important for tum or angiogenesis in melanoma xenografts.