β3GnT8 plays an important role in CD147 signal transduction as an upstream modulator of MMP production in tumor cells

Abstract. Aberrant carbohydration by related glycosyl-transferases plays an important role in the progression of cancer. This study focused on the ablity of β-1,3- N -acetyl-glucosaminyltransferase-8 (β3GnT8) to regulate MMP-2 expression through regulation of the CD147 signal transduc-tion pathway in cancer cells. β3GnT8 catalyzes and then extends a polylactosamine chain specifically on β1-6-branched tetraantennary N-glycans. CD147 is a major carrier of β1-6-branched polylactosamine sugars on tumor cells, and the high glycoform of CD147 (HG-CD147) induces matrix metallopro -teinase (MMP) production. In the present study, we analyzed β3GnT8 mRNA expression in 6 cancer cell lines (MCF-7, M231, LN229, U87, SGC-7901 and U251). We found that β3GnT8 expression in the LN229, SGC-7901 and U251 cell lines was higher than that in the other cell lines. Therefore, we established β3GnT8-knockdown cell lines derived from the LN229 and SGC-7901 cell lines to examine the level of poly-lactosamine and CD147 N-glycosylation. In addition, tunicamycin is widely used as an inhibitor of N-linked glyco-sylation. Hence, various concentrations of tunicamycin were used to treat the cells in order to study its influence on CD147 N-glycosylation and MMP-2 expression. In conclusion, we found that β3GnT8 regulated the level of N-glycans on CD147 and that N-glycosylation of CD147 has an important effect on MMP-2 expression. Our findings suggest that β3GnT8 affects the signal transduction pathway of MMP-2 by altering the N-glycan structure of CD147.