Abstract
BackgroundThe prognosis of most hepatocellular carcinoma (HCC) patients is poor due to the high metastatic rate of the disease. Understanding the molecular mechanisms underlying HCC metastasis is extremely urgent. The role of CD24 and NDRG2 (N-myc downstream-regulated gene 2), a candidate tumor suppressor gene, has not yet been explored in HCC.MethodsThe mRNA and protein expression of CD24 and NDRG2 was analyzed in MHCC97H, Huh7 and L-02 cells. Changes in cell adhesion, migration and invasion were detected by up- or down-regulating NDRG2 by adenovirus or siRNA. The expression pattern of NDRG2 and CD24 in HCC tissues and the relationship between NDRG2 and HCC clinical features was analyzed by immunohistochemical and western blotting analysis.ResultsNDRG2 expression was negatively correlated with malignancy in HCC. NDRG2 exerted anti-tumor activity by regulating CD24, a molecule that mediates cell-cell interaction, tumor proliferation and adhesion. NDRG2 up-regulation decreased CD24 expression and cell adhesion, migration and invasion. By contrast, NDRG2 down-regulation enhanced CD24 expression and cell adhesion, migration and invasion. Immunohistochemical analysis of 50 human HCC clinical specimens showed a strong correlation between NDRG2 down-regulation and CD24 overexpression (P = 0.04). In addition, increased frequency of NDRG2 down-regulation was observed in patients with elevated AFP serum level (P = 0.006), late TNM stage (P = 0.009), poor differentiation grade (P = 0.002), tumor invasion (P = 0.004) and recurrence (P = 0.024).ConclusionsOur findings indicate that NDRG2 and CD24 regulate HCC adhesion, migration and invasion. The expression level of NDRG2 is closely related to the clinical features of HCC. Thus, NDRG2 plays an important physiological role in HCC metastasis.
Highlights
The prognosis of most hepatocellular carcinoma (HCC) patients is poor due to the high metastatic rate of the disease
Cells were exposed to siRNA in Dulbecco’s Modified Eagle’s Medium (DMEM) for 6 h, after which the medium was replaced with DMEM containing 10% fetal bovine serum (FBS) and the cells were incubated for 48 h
NDRG2 and CD24 expression in HCC and normal liver cells The expression of NDRG2 and CD24 was examined in three liver cell lines
Summary
The prognosis of most hepatocellular carcinoma (HCC) patients is poor due to the high metastatic rate of the disease. The role of CD24 and NDRG2 (N-myc downstream-regulated gene 2), a candidate tumor suppressor gene, has not yet been explored in HCC. Invasion and metastasis are closely linked with poor prognosis and death in HCC. Molecules capable of inhibiting invasion and metastasis are attractive candidates for targeted therapy. AF159092), initially identified in our laboratory, The mechanisms by which NDRG2 inhibits the aggressive behavior of HCC are not fully understood. Adhesion molecules involved in HCC metastasis were screened for possible contribution to NDRG2-mediated tumor inhibition. CD24 is overexpressed in aggressive HCC cell lines and in the tumor tissues of patients with recurrent HCC. CD24 mRNA overexpression correlates strongly with p53 gene mutation and poor HCC differentiation [18]. CD24 is a novel molecule involved in HCC tumorigenesis and metastasis
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