The molecular mechanism underlying angiogenesis in hepatocellular carcinoma: the imbalance activation of signaling pathways

<正> OBJECTIVE: To explore the effect of two dominating signaling pathways, VEGF/KDR andangiopoietins/Tie2, on the formation of new blood vessel in hepatocellular carcinoma (HCC) growth andmetastasis.METHODS: RT-PCR and Western blot were employed to evaluate the VEGF/KDR andangiopoietins/Tie2 expression in samples from 23 patients with HCC. Meanwhile, microvessel density(MVD) was determined as a marker of angiogenesis by counting CD34 positive cells with the method ofimmunohistochemistry.RESULTS: The two pathways were activated in all HCC samples. The expressions of vascular endothelialgrowth factor (VEGF) and angiopoietin-2 (Ang2) were significantly higher (P<0.05) in hepatocellularcarcinoma tissues and the margin of the tumor than those in control groups, and so did CD34 positivecells. Although significant difference in the expression of kinase insert domain containing receptor (KDR)and Ang1/Tie2 was not observed in all groups, their distinct high levels were seen in hepatoma and itsmargin compared with normal and cirrhotic liver. VEGF and Ang2 expressions were seen up-regulated inHCC with vascular invasion and satellite lesion.CONCLUSIONS: The two signaling pathways, VEGF/KDR and angiopoietins/Tie2 are activated in theprocess of angiogenesis in HCC and modulate the formation of new blood vessels. The imparity of the twosignaling pathways’ activation is to benefit HCC metastasis. In the two pathways, VEGF and Ang2 mayplay an important role in the process of angiogenesis, and are necessary indicators for the prognosis andmetastasis of HCC. This study provides another clue for the exploration of anti-angiogenic agents.