Increased expression of vascular endothelial growth factor in small hepatocellular carcinoma

Abstract

Vascular endothelial growth factor (VEGF) is involved in both development and progression of several epithelial tumours, but its role in hepatocellular carcinoma (HCC) is unclear. Assessment of liver and blood levels of VEGF may provide further insights on angiogenesis in HCC. Tissue mRNA of VEGF-165, VEGF-189 and their receptor KDR was assessed by a semi-quantitative retro-transcriptase polymerase chain reaction, and expressed as target transcript/beta-actin ratio, in 29 patients with HCC, 26 with cirrhosis and 15 with chronic hepatitis. VEGF-165 was also measured by ELISA in plasma samples obtained from both hepatic and femoral veins in additional 58 patients, including 15 with HCC. The liver expression of mRNA of VEGF-165, VEGF-189 and KDR was higher in HCC than in chronic liver diseases (1.54 +/- 0.89 vs 0.62 +/- 0.47, P < 0.0001; 1.09 +/- 0.65 vs 0.64 +/- 0.54, P = 0.003; 1.30 +/- 1.09 vs 0.69 +/- 0.72, P = 0.014). VEGF-165 was higher in HCC tissue than in extra-tumoural tissues (1.44 +/- 0.31 vs 1.03 +/- 0.21, P = 0.0009) and in the cirrhotic tissue of HCC patients than in HCC-free cirrhosis (1.03 +/- 0.23 vs 0.45 +/- 0.45, P = 0.0002). Tissue VEGF-189 mRNA inversely correlated with tumour size and degree of tumour cell proliferation. The hepatic and femoral vein levels of VEGF-165 protein were significantly higher in HCC patients than in cirrhotic patients (66.7 +/- 57.1 vs 24.2 +/- 16.4 pg/mL, P = 0.0001 and 37.1 +/- 42.2 vs 13.5 +/- 9.6 pg/mL, P = 0.001). There was a gradient of VEGF-165 between hepatic and femoral veins in both HCC and cirrhosis. In conclusion, VEGF appears to be involved in the development of HCC and it could be a predictor of HCC development in patients with cirrhosis.

Reversal of elastase-induced pulmonary emphysema and promotion of alveolar epithelial cell proliferation by simvastatin in mice

“…The presence or absence of airway inflammation induced by elastase instillation may account for the differential mobilization of VEGF between the protocols. Previous reports suggested that the VEGF concentration gradients in vivo may promote local enhancement of angiogenesis (13,14,21). It was interesting that VEGF concentration gradients between the lung and circulation appeared to be enhanced by SS in our murine emphysema model.…”

Vascular endothelial growth factor in the management of hepatocellular carcinoma

“…35,36 Similar findings in other studies have laid the groundwork for using VEGF activity as a tool to screen for both premalignant liver lesions and invasive HCC. 37,38 In the first study, 37 tissue mRNA level of VEGF-165 was assessed by a semiquantitative reversetranscriptase polymerase chain reaction in 29 patients with HCC, 26 with cirrhosis, and 15 with chronic hepatitis. The liver expression of mRNA of VEGF-165 was found to be significantly higher in HCC than in chronic liver diseases and in the cirrhotic tissue of HCC patients than in those with HCC-free cirrhosis.…”

Circulating vascular endothelial growth factor and nitric oxide in patients with liver cirrhosis: A possible association with liver function impairment

“…More recently Fernandez et al (37) showed in portal vein ligated rats that treatment with rapamycin (VEGF signaling inhibitor) and Gleevec (PDGF signaling inhibitor) reduced splanchnic neovascularization and significantly decreased portal pressure. Furthermore, Iavarone et al (38) showed a significant VEGF gradient between hepatic vein and peripheral vein serum levels that correlated with the degree of hepatic vein pressure gradient (HVPG) in hepatocellular carcinoma (HCC)-free patients. Interestingly, such association was not found in patients with cirrhosis and HCC, suggesting, that in these patients serum levels of VEGF were mainly influenced by VEGF synthesis by neoplastic liver cells rather than by portal hypertension.…”