Glycan-related gene expression signatures in human metastatic hepatocellular carcinoma cells

Abstract

Abstract. 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.

Cell Surface Glycan Alterations in Epithelial Mesenchymal Transition Process of Huh7 Hepatocellular Carcinoma Cell

“…A higher level of expression of sLe a indicates stronger tumor invasion [36]. Consistent with previous study [15], the β3GalT5 glycogene was increased in the HCC EMT model; it implied that β3GalT5 and its product may play an important role in the development and metastasis of HCC.…”

“…It is responsible to form the glycosidic bound by adding β1, 3Gal residues to GlcNAcβ1-3Galβ1-4GlcNAcβ1-R branched and then generated sLe a structure which was bound by lectin AAL. Our previous study [15] found that β3GalT5 glycogene was up-regulated in high metastatic potential HCCLM3 cells by glycogene microarray. After knocking out β3GalT5, the ability of invasion and migration for HCCLM3 cells were decreased significantly.…”

Discovery of Specific Metastasis-Related N-Glycan Alterations in Epithelial Ovarian Cancer Based on Quantitative Glycomics

“…Song et al reported that the bisecting GlcNAc on N -glycans inhibited growth factor signaling and retarded mammary tumor progression [32]. However, MGAT3 was reported upregulated in high metastatic human hepatocarcinoma cell line HCCLM3 in comparison with cell line with low metastatic potential [66]. Overexpression of MGAT3 in HeLaS3 cells enhanced the epidermal growth factor (EGF) mediated cell signaling [67], and transfecting myelogenous leukemia cell line K562 with MGAT3 protected it from natural killer cytotoxicity and increased spleen colonization [68].…”

B4GALT family mediates the multidrug resistance of human leukemia cells by regulating the hedgehog pathway and the expression of p-glycoprotein and multidrug resistance-associated protein 1

“…1 It has shown that oligosaccharide expression may be associated with carcinogenesis, metastasis and development of chemoresistance of malignant cells. 2, 3, 4 Although the alterations of glycan structures are observed in drug resistance leukemia cells, 5, 6 there is limited report about the effects of GTs and corresponding glycogenes in the development of leukemia drug resistance.…”