Expression of NOTCH4 affects vasculogenic mimicry formation in hepatocellular carcinoma / 临床肝胆病杂志

ABSTRACT

ObjectiveTo investigate the effect of NOTCH4 expression on vasculogenic mimicry (VM) formation in hepatocellular carcinoma (HCC). MethodsTumor tissues were collected from 85 patients diagnosed with HCC. The relationship between NOTCH4 expression and VM was examined using immunohistochemical staining and PAS/CD31 double staining. The influence of siRNA-mediated NOTCH4 silencing on VM network formation in HCC was observed in the 3D cell culture system in vitro. Experimental data were assessed with Mann-Whitney U test and one-way analysis of variance. ResultsNOTCH4 had significantly higher expression in VM-positive HCC tissues than in VM-negative HCC tissues (P=0.019). In siRNA-treated cells, NOTCH4 mRNA and protein expression was significantly down-regulated compared with those in mock-treated cells (P=0.007; P=0.003) and untreated cells (P=0.000; P=0.000). VM network formation was impaired by inhibition of NOTCH4 expression in the 3D cell culture system. ConclusionNOTCH4 plays an important role in VM formation in HCC and may provide a novel molecular target for anti-angiogenesis therapy for HCC.