Kang Xiaonan, Wang Nian, Pei Chen, Sun Lu, Sun Ruixia, Chen Jie, Liu Yinkun
Liver Cancer Institute of Zhongshan Hospital and Institute of Biomedical Science, Fudan University, Shanghai;
Exp Ther Med. 2012 Mar;3(3):415-422. doi: 10.3892/etm.2011.430. Epub 2011 Dec 23.
Human hepatocellular carcinoma (HCC) ranks second in cancer mortality in China; recurrence and metastasis have been the cause of the high mortality. Glycans on the cell surface play a pivotal role in tumor metastasis. The global alteration in the structure and composition of N-glycans during HCC metastasis remains unknown. To understand glycan alterations of glycoproteins by correlating the glycosyltransferase expression profile with glycan structure, we systematically used glycan profiling tools: glycogene microarray analyses of 115 genes, including glycotransferases, glycosidases and nuclear sugar transporters and lectin chips to investigate the glycan-related gene expression signatures in the high metastatic potential HCC cell line, HCCLM3, in comparison to the HCC cell line, Hep3B, with low metastatic potential. Of the 115 genes, 18 genes were up-regulated in high metastatic potential HCCLM3 cells in comparison to Hep3B cells, while 11 genes were down-regulated. The differentially expressed genes, such as ST3GalI, FUT8, β3GalT5, MGAT3 and MGAT5, were mainly involved in the synthesis of N-glycan and glycolipids, particularly the sialyl Lewis antigen. The results of the glycogene microarray analysis were further validated by quantitative real-time PCR analysis and lectin-based analysis. The differentially expressed glycogenes identified in this study may provide new insights and represent novel factors for investigating the functional role of cell surface carbohydrate-mediated HCC metastasis.
在中国，人类肝细胞癌（HCC）的癌症死亡率位居第二；复发和转移一直是高死亡率的原因。细胞表面的聚糖在肿瘤转移中起关键作用。HCC转移过程中N - 聚糖结构和组成的整体变化尚不清楚。为了通过将糖基转移酶表达谱与聚糖结构相关联来了解糖蛋白的聚糖变化，我们系统地使用了聚糖分析工具：对115个基因进行糖基因微阵列分析，包括糖基转移酶、糖苷酶和核苷糖转运蛋白，并使用凝集素芯片，以研究高转移潜能的HCC细胞系HCCLM3与低转移潜能的HCC细胞系Hep3B中与聚糖相关的基因表达特征。在这115个基因中，与Hep3B细胞相比，18个基因在高转移潜能的HCCLM3细胞中上调，而11个基因下调。差异表达的基因，如ST3GalI、FUT8、β3GalT5、MGAT3和MGAT5，主要参与N - 聚糖和糖脂的合成，特别是唾液酸化路易斯抗原。糖基因微阵列分析的结果通过定量实时PCR分析和基于凝集素的分析进一步验证。本研究中鉴定出的差异表达糖基因可能为研究细胞表面碳水化合物介导的HCC转移的功能作用提供新的见解，并代表新的因素。
