High expression of β3GnT8 is associated with the metastatic potential of human glioma

Changes in glycosylation due to specific alterations of glycosyltransferase activity have been shown in various tumor cells, including human glioma cells. β1,3-N-acetylglucosaminyltransferase-8 (β3GnT8) catalyzes the formation of polylactosamine on β1–6 branched N-glycans. Upregulated expression of β3GnT8 was described in some tumors, but its precise role in regulating glioma invasion and metastasis remains unclear. In this study, we report on an investigation of the expression of β3GnT8 in human glioma by immunohistochemical analysis. Out of 42 glioma tissues, 37 (88.1%) showed positive β3GnT8 expression, which was significantly higher than that in normal brain tissues (P<0.001). Additionally, the level of β3GnT8 increased with increased pathological grade of gliomas. Silencing of β3GnT8 in U251 glioma cells attenuated the formation of polylactosamine, and decreased cell proliferation, migration and metastatic ability in vitro and in vivo. By contrast, the overexpression of β3GnT8 in U251 cells exhibited enhanced metastatic potential. A positive correlation between β3GnT8 and matrix metalloproteinase-2 (MMP-2) expression in U251 cells was also observed. The results demonstrated a critical role of β3GnT8 in the metastatic potential of glioma cells, indicating that manipulating β3GnT8 expression may have therapeutic potential for the treatment of malignant glioma.