β3GnT8 regulates the metastatic potential of colorectal carcinoma cells by altering the glycosylation of CD147

Ni,Jianlong; Jiang,Zhi; Shen,Li; Gao,Liping; Yu,Meiyun; Xu,Xu; Zou,Shitao; Hua,Dong; Wu,Shiliang

doi:10.3892/or.2014.3042

β3GnT8 regulates the metastatic potential of colorectal carcinoma cells by altering the glycosylation of CD147

Authors:
- Jianlong Ni
- Zhi Jiang
- Li Shen
- Liping Gao
- Meiyun Yu
- Xu Xu
- Shitao Zou
- Dong Hua
- Shiliang Wu
View Affiliations

Affiliations: Department of Biochemistry and Molecular Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China, The Fourth Affiliated Hospital of Soochow University, Wuxi, Jiangsu 214062, P.R. China
Published online on: February 20, 2014 https://doi.org/10.3892/or.2014.3042
Pages: 1795-1801

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Aberrant glycosylation of cell surface glycoproteins is commonly associated with the invasion and metastasis of colorectal carcinomas, which can be attributed to the upregulated expression of glycosyltransferases. Therefore, elucidation of glycosyltransferases and their substrates may improve our understanding of their roles in tumor metastasis. β-1,3-N-acetylglucosaminyltransferase-8 (β3GnT8) is a key enzyme that catalyzes the formation of poly-N-acetyllactosamine (polylactosamine) chains on β1,6-branched N-glycans in vitro, which is also involved in tumor invasion. In the present study, we analyzed the expression of β3GnT8 and its product polylactosamine in four human colorectal carcinoma cell lines (LS-174T, SW620, SW480 and LoVo) with different metastatic potential. We found that the levels of β3GnT8 and polylactosamine chains were gradually increased in the colorectal cancer cell lines in a trend from low to high metastatic potential. Notably, a significantly positive relationship between β3GnT8 expression and HG-CD147 was noted in the colorectal cancer cell lines. To further investigate their relationships, exogenous β3GnT8 was introduced into the LS-174T cells, while expression of β3GnT8 was downregulated in the LoVo cells. The overexpression of β3GnT8 in LS-174T cells increased the level of HG-CD147. Conversely, downregulation of β3GnT8 expression in LoVo cells significantly decreased the expression of HG-CD147. HG-CD147 is a major carrier of β1,6-branched polylactosamine sugars; therefore, the regulation of β3GnT8 significantly altered the β1,6-branched polylactosamine structures on CD147. Hence, we suggest that β3GnT8 plays a key role in the metastasis of colorectal cancer cells by altering the β1,6-branched polylactosamine sugars of CD147.

View Figures

View References

1	Demetriou M, Granovsky M, Quaggin S and Dennis JW: Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation. Nature. 409:733–739. 2001. View Article : Google Scholar : PubMed/NCBI
2	Dennis JW, Granovsky M and Warren CE: Glycoprotein glycosylation and cancer progression. Biochim Biophys Acta. 1473:21–34. 1999. View Article : Google Scholar : PubMed/NCBI
3	Saitoh O, Wang WC, Lotan R and Fukuda M: Differential glycosylation and cell surface expression of lysosomal membrane glycoproteins in sublines of a human colon cancer exhibiting distinct metastatic potentials. J Biol Chem. 267:5700–5711. 1992.
4	Figer A, Perez-Staub N, Carola E, et al: FOLFOX in patients aged between 76 and 80 years with metastatic colorectal cancer: an exploratory cohort of the OPTIMOX1 study. Cancer. 110:2666–2671. 2007.PubMed/NCBI
5	Mansouri D, McMillan DC, Crighton EM and Horgan PG: Screening for colorectal cancer: what is the impact on the determinants of outcome? Crit Rev Oncol Hematol. 85:342–349. 2013. View Article : Google Scholar : PubMed/NCBI
6	Ishida H, Togayachi A, Sakai T, et al: A novel β1,3-N-acetylglucosaminyltransferase (β3Gn-T8), which synthesizes poly-N-acetyllactosamine, is dramatically upregulated in colon cancer. FEBS Lett. 579:71–78. 2005.
7	Shen L, Liu Z, Tu Y, Xu L, Sun X and Wu S: Regulation of MMP-2 expression and activity by β-1,3-N-acetylglucosaminyltransferase-8 in AGS gastric cancer cells. Mol Biol Rep. 38:1541–1550. 2011.
8	Polette M, Gilles C, Marchand V, et al: Tumor collagenase stimulatory factor (TCSF) expression and localization in human lung and breast cancers. J Histochem Cytochem. 45:703–709. 1997. View Article : Google Scholar : PubMed/NCBI
9	Ellis SM, Nabeshima K and Biswas C: Monoclonal antibody preparation and purification of a tumor cell collagenase-stimulatory factor. Cancer Res. 49:3385–3391. 1989.PubMed/NCBI
10	Yu XL, Jiang JL, Li L, Feng Q, Xu J and Chen ZN: The glycosylation characteristic of hepatoma-associated antigen HAb18G/CD147 in human hepatoma cells. Int J Biochem Cell Biol. 38:1939–1945. 2006. View Article : Google Scholar : PubMed/NCBI
11	Sun J and Hemler ME: Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions. Cancer Res. 61:2276–2281. 2001.PubMed/NCBI
12	Carvalho FC, Soares SG, Tamarozzi MB, Rego EM and Roque-Barreira MC: The recognition of N-glycans by the lectin ArtinM mediates cell death of a human myeloid leukemia cell line. PLoS One. 6:e278922011. View Article : Google Scholar : PubMed/NCBI
13	Naka R, Kamoda S, Ishizuka A, Kinoshita M and Kakehi K: Analysis of total N-glycans in cell membrane fractions of cancer cells using a combination of serotonin affinity chromatography and normal phase chromatography. J Proteome Res. 5:88–97. 2006. View Article : Google Scholar
14	Mitsui Y, Yamada K, Hara S, Kinoshita M, Hayakawa T and Kakehi K: Comparative studies on glycoproteins expressing polylactosamine-type N-glycans in cancer cells. J Pharm Biomed Anal. 70:718–726. 2012. View Article : Google Scholar : PubMed/NCBI
15	Huang C, Zhou J, Wu S, Shan Y, Teng S and Yu L: Cloning and tissue distribution of the human B3GALT7 gene, a member of the beta1,3-glycosyltransferase family. Glycoconj J. 21:267–273. 2004. View Article : Google Scholar : PubMed/NCBI
16	Yamamoto H, Swoger J, Greene S, et al: β1,6-N-acetylglucosamine-bearing N-glycans in human gliomas: implications for a role in regulating invasivity. Cancer Res. 60:134–142. 2000.
17	Fernandes B, Sagman U, Auger M, Demetrio M and Dennis JW: β1–6 branched oligosaccharides as a marker of tumor progression in human breast and colon neoplasia. Cancer Res. 51:718–723. 1991.
18	Hakomori S: Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. Cancer Res. 56:5309–5318. 1996.PubMed/NCBI
19	van den Eijnden DH, Koenderman AH and Schiphorst WE: Biosynthesis of blood group i-active polylactosaminoglycans. Partial purification and properties of an UDP-GlcNAc:N-acetyllactosaminide β1→3-N-acetylglucosaminyltransferase from Novikoff tumor cell ascites fluid. J Biol Chem. 263:12461–12471. 1988.PubMed/NCBI
20	Flatmark K, Maelandsmo GM, Martinsen M, Rasmussen H and Fodstad O: Twelve colorectal cancer cell lines exhibit highly variable growth and metastatic capacities in an orthotopic model in nude mice. Eur J Cancer. 40:1593–1598. 2004. View Article : Google Scholar : PubMed/NCBI
21	Kusakai G, Suzuki A, Ogura T, Kaminishi M and Esumi H: Strong association of ARK5 with tumor invasion and metastasis. J Exp Clin Cancer Res. 23:263–268. 2004.PubMed/NCBI
22	Seko A and Yamashita K: Activation of β1,3-N-acetylglucosaminyltransferase-2 (beta3Gn-T2) by β3Gn-T8. Possible involvement of β3Gn-T8 in increasing poly-N-acetyllactosamine chains in differentiated HL-60 cells. J Biol Chem. 283:33094–33100. 2008.
23	Krishnan V, Bane SM, Kawle PD, Naresh KN and Kalraiya RD: Altered melanoma cell surface glycosylation mediates organ specific adhesion and metastasis via lectin receptors on the lung vascular endothelium. Clin Exp Metastasis. 22:11–24. 2005. View Article : Google Scholar
24	Demetriou M, Nabi IR, Coppolino M, Dedhar S and Dennis JW: Reduced contact-inhibition and substratum adhesion in epithelial cells expressing GlcNAc-transferase V. J Cell Biol. 130:383–392. 1995. View Article : Google Scholar : PubMed/NCBI
25	Tang W, Chang SB and Hemler ME: Links between CD147 function, glycosylation, and caveolin-1. Mol Biol Cell. 15:4043–4050. 2004. View Article : Google Scholar : PubMed/NCBI
26	Guo H, Zucker S, Gordon MK, Toole BP and Biswas C: Stimulation of matrix metalloproteinase production by recombinant extracellular matrix metalloproteinase inducer from transfected Chinese hamster ovary cells. J Biol Chem. 272:24–27. 1997. View Article : Google Scholar
27	Zucker S, Hymowitz M, Rollo EE, et al: Tumorigenic potential of extracellular matrix metalloproteinase inducer. Am J Pathol. 158:1921–1928. 2001. View Article : Google Scholar : PubMed/NCBI
28	Caudroy S, Polette M, Nawrocki-Raby B, et al: EMMPRIN-mediated MMP regulation in tumor and endothelial cells. Clin Exp Metastasis. 19:697–702. 2002. View Article : Google Scholar : PubMed/NCBI
29	Fan J, Wang S, Yu S, He J, Zheng W and Zhang J: N-acetylglucosaminyltransferase IVa regulates metastatic potential of mouse hepatocarcinoma cells through glycosylation of CD147. Glycoconj J. 29:323–334. 2012. View Article : Google Scholar : PubMed/NCBI
30	Huang W, Luo WJ, Zhu P, et al: Modulation of CD147-induced matrix metalloproteinase activity: role of CD147 N-glycosylation. Biochem J. 449:437–448. 2013. View Article : Google Scholar : PubMed/NCBI