VEGF participates in neovascularization and sinusoidal capillarization in HCC

Early in hepatocarcinogenesis, hepatocellular carcinoma do not show hyperva scularity, at later stages, they require abundant arterial blood supply. Va scular endothelial growth factor is one of the most directly-acting angioge nic factors. At this time, we clarified the participation of vascular endot helial growth factor in the development of neovascularization and sinusoida l capillarization in hepatocellular carcinoma. Vascular endothelial growth factor expression was detected in hepatoma cell s and hepatic stellate cells by immunoelectron microscopy and in situ hybri dization. The major vascular endothelial growth factor isoforms expressed i n hepatocellular carcinoma were vascular endothelial growth factor 121 and 165. The expression of flt-1 and KDR/flk-1 in hepatocellular carcinoma was also confirmed by RT-PCR. In hepatocellular carcinomas with hypervascularit y, type IV collagen and laminin were present corresponding to basement memb ranes along the sinusoidal endothelial cells, which had few fenestrae. In h epatocellular carcinomas without hypervascularity, although type IV collage n was present along the sinusoidal endothelial cells that had a few fenestr ae, laminin as well as basement membranes were rarely detected. Vascular en dothelial growth factor expression in hepatocellular carcinomas with hyperv ascularity was stronger than in those not showing hypervascularity, In in v itro study, increased expression of vascular endothelial growth factor mRNA in hepatoma cells was observed under the condition of hypoxia. These results suggest that vascular endothelial growth factor participates in the development of neovascularization and sinusoidal capillarization in hepatocellular carcinoma.