Regulation of angiogenesis in human hepatomas: possible involvement of p53-inducible inhibitor of vascular endothelial cell proliferation

Mechanisms regulating angiogenesis in human hepatomas were analyzed. Huh7 hepatoma cells transplanted into athymic mice formed highly vascularized reddish tumors with abundant microvessels, while angiogenesis by PLC/PRF/5 hepatoma cells was less remarkable. However, the production of angiogenesis stimulators such as VEGF and IL6 by Huh7 cells was much less than by PLC/PRF/5 cells. In addition, the production of angiogenesis inhibitor TSP-1 by Huh7 cells was greater than by PLC/PRF/5 cells. Therefore, the difference in angiogenesis between these two hepatomas was not explained by the production of these known angiogenesis regulators. On the other hand, PLC/PRF/5 cells but not Huh7 cells secreted an inhibitor of the proliferation of vascular endothelial cells, which was enhanced by p53-gene transfer. These results suggest that the production of this p53-inducible angiogenesis inhibitor is responsible, at least partly, for the regulation of angiogenesis in human hepatomas.