Zhou Zhenzhen, Deng Huan, Yan Wei, Huang Huanjun, Deng Yueling, Li Yuan, Tian De'an
Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
J Huazhong Univ Sci Technolog Med Sci. 2012 Jun;32(3):353-357. doi: 10.1007/s11596-012-0061-3. Epub 2012 Jun 9.
Metastasis contributes to the poor prognosis of hepatocellular carcinoma (HCC). However, the mechanism through which a primary HCC cell develops into a metastatic phenotype is not well understood. The purpose of this study was to examine the correlation between metadherin (MTDH)/astrocyte elevated gene-1 (AEG-1) expression in HCC cell lines of different metastatic potentials and such metastatic phenotypes as orientation chemotaxis and adhesion. MTDH/AEG-1 expression was detected by RT-PCR and western blotting in HCC cell lines (HepG2, Huh7, Sk-HEP-1, MHCC-97H). Distribution of MTDH/AEG-1 was observed by immunofluorescence staining and confocal laser scanning microscopy. The abilities of orientation chemotaxis and adhesion and the index of interaction between HCC cell lines and microvascular endothelial cell lines (MVECs, including HUVECs and HPMECs) were measured by chemotaxis assay and adhesion assay, respectively. The results showed that MTDH/AEG-1 protein expression was significantly higher in high metastatic potential cancer cell lines (Sk-HEP-1, MHCC-97H) than in low metastatic potential cell lines (HepG2, Huh7) (P<0.05). The MTDH/AEG-1 protein was localized in the perinuclear region of HCC cells. Furthermore, the abilities of orientation chemotaxis and adhesion of HCC cells to HPMECs were increased as compared with those of HCC cells to HUVECs (P<0.05). The abilities of orientation chemotaxis and adhesion were much stronger in Sk-HEP-1 and MHCC-97H cells with MTDH/AEG-1 highly expressed than in HepG2 and Huh7 cells with MTDH/AEG-1 lowly expressed (P<0.05). These results suggested that the expression of MTDH/AEG-1 gene in HCC cell lines of different metastatic potentials was closely positively related to the abilities of orientation chemotaxis and adhesion of HCC cells. It was deduced that MTDH/AEG-1 might play a pivotal role in the lung-specific metastasis of HCC, which may be mediated through orientation chemotaxis and adhesion abilities of HCC cells. MTDH/AEG-1 may serve as a potential therapeutic target for HCC.
转移导致肝细胞癌（HCC）预后不良。然而，原发性肝癌细胞发展为转移表型的机制尚不清楚。本研究旨在探讨不同转移潜能的肝癌细胞系中黏附素（MTDH）/星形胶质细胞上调基因1（AEG-1）表达与趋化性定向和黏附等转移表型之间的相关性。通过RT-PCR和蛋白质印迹法检测肝癌细胞系（HepG2、Huh7、Sk-HEP-1、MHCC-97H）中MTDH/AEG-1的表达。通过免疫荧光染色和共聚焦激光扫描显微镜观察MTDH/AEG-1的分布。分别采用趋化性实验和黏附实验检测肝癌细胞系与微血管内皮细胞系（MVECs，包括人脐静脉内皮细胞（HUVECs）和人肺微血管内皮细胞（HPMECs））之间的趋化性定向、黏附能力及相互作用指数。结果显示，高转移潜能癌细胞系（Sk-HEP-1、MHCC-97H）中MTDH/AEG-1蛋白表达明显高于低转移潜能细胞系（HepG2、Huh7）（P<0.05）。MTDH/AEG-1蛋白定位于肝癌细胞的核周区域。此外，与肝癌细胞与人脐静脉内皮细胞的相互作用相比，肝癌细胞与人肺微血管内皮细胞的趋化性定向和黏附能力增强（P<0.05）。MTDH/AEG-1高表达的Sk-HEP-1和MHCC-97H细胞的趋化性定向和黏附能力比MTDH/AEG-1低表达的HepG2和Huh7细胞更强（P<0.05）。这些结果表明，不同转移潜能的肝癌细胞系中MTDH/AEG-1基因的表达与肝癌细胞的趋化性定向和黏附能力密切正相关。推测MTDH/AEG-1可能在肝癌的肺特异性转移中起关键作用，这可能是通过肝癌细胞的趋化性定向和黏附能力介导的。MTDH/AEG-1可能成为肝癌潜在的治疗靶点。
