Tumorigenicity depends on angiogenic potential of tumor cells: dominant role of vascular endothelial growth factor and/or fibroblast growth factors produced by tumor cells.

The aim of this study was to determine the role of tumor-derived angiogenic factors in solid tumor formation. We compared the angiogenic potential of tumorigenic and non-tumorigenic human tumor cell lines. All tumorigenic cell lines induced angiogenesis in vivo and their angiogenesis-inducing abilities were higher than those of the other non-tumorigenic cell lines. This in vivo angiogenic potential was well correlated with the in vitro endothelial cell growth-stimulating activity contained in the cell extract or conditioned medium of each cell line. The endothelial cell growth-stimulating activities of these cell lines were completely inhibited by neutralizing antibodies to basic fibroblast growth factor (bFGF), acidic FGF (aFGF) or vascular endothelial growth factor (VEGF). Furthermore, the levels of tumor-derived endothelial cell growth-stimulating activities depended on the amounts of angiogenic factors such as VEGF and bFGF produced by tumor cells. Although VEGF transcripts were detected in all of the cell lines by RT-PCR assay, the non-tumorigenic cell lines showed poor productivity of VEGF as well as FGFs and had less or non-potency for endothelial cell growth stimulation. These findings suggest that the increase in production of angiogenic factors by tumor cells is necessary for their in vivo angiogenic and tumorigenic potentials, and that VEGF and FGFs are the major mediators of tumor-induced angiogenesis.