INCREASED EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR IN HUMAN HEPATOCELLULAR-CARCINOMA

Background/Aims: Angiogenesis is critical for the development and prog ression of solid tumors. the purpose of this study was to evaluate the possible role of vascular endothelial growth factor (which is conside red to be one of the most important factors involved in tumor-associat ed angiogenesis), in human hepatocellular carcinoma. Methods: Vascular endothelial growth factor gene and protein expression were analyzed b y means of Northern hybridization and immunohistochemical methods in 5 hepatocellular carcinoma cell lines. Secretion of vascular endothelia l growth factor was evaluated by immunoblotting of conditioned medium of these hepatocellular carcinoma cells. Further, we compared the leve l of vascular endothelial growth factor expression in hepatocellular c arcinoma tissues along with that in surrounding tumor-free tissues obt ained from 20 patients. We also analyzed mRNA expression of Flt-1, one of the vascular endothelial growth factor specific high-affinity rece ptors, in hepatocellular carcinoma cell lines. Results: Northern hybri dization analysis and immunohistochemistry revealed that all cultured hepatocellular carcinoma cells exhibited a high level of vascular endo thelial growth factor mRNA. In addition, vascular endothelial growth f actor secretion by Hep G2, one of the hepatocellular carcinoma cell li nes, was shown by Western blot. In vivo, we observed vascular endothel ial growth factor expression in both hepatocellular carcinoma and non- hepatocellular carcinoma tissues. However, in 12 of 20 cases, vascular endothelial growth factor mRNA levels were significantly up-regulated in hepatocellular carcinoma tissues. In the majority of cases (10 out of 12 cases) with abundant tumor vascularity, vascular endothelial gr owth factor mRNA up-regulation in hepatocellular carcinoma tissues was observed. We failed to detect Flt-1 mRNA expression in hepatocellular carcinoma cells. Conclusions: this study suggests that the possibilit y that hepatocellular carcinoma cells overexpress the vascular endothe lial growth factor gene and protein. The findings support the hypothes is that vascular endothelial growth factor is one of the important fac tors involved in the angiogenesis of hepatocellular carcinoma, and may even be involved in the development and/or progression of hepatocellu lar carcinoma itself.