Cosmc transfection decreases malignant behavior of Tn cells and enhances sensitivity to apoptosis when induced by Apo2L/TRAIL via alteration of O-glycan structure.

Cosmc mutations may cause abnormal O-glycosylation and result in Tn antigen expression. In the current study, it was discovered that proliferation and migration of Tn+ cells (Jurkat T and LS174T-Tn cells) with mutant Cosmc decreased after transfected Cosmc, and their sensitivity to apoptosis induced by Apo2L/TRAIL increased. Core 1-, 2-, and 3-derived O-glycans were absent in Tn cells. After Cosmc transfection, normal extended core 1-derived O-glycans appeared and were accompanied by increased T-synthase activity. Core 2-derived O-glycans appeared in transfected LS174T-Tn cells, and their structural types and levels were lower than those in LS174T-Tn cells. Core 3-derived O-glycans were present only in LS174T-Tn cells. The activity of C3GnT in LS174T-Tn cells was lower than that in LS174T-Tn cells, and it was absent in Jurkat T cells. Cosmc transfection did not alter C3GnT activity or core 3-derived O-glycans in Jurkat T and LS174T-Tn cells. The results demonstrated that the composition and structure of O-glycans were different among various Tn cells, which not only affected cell malignant behavior but also modulated sensitivity to apoptotic stimuli. Thus, Cosmc transfection may effectively decrease the malignant behavior of Tn tumor cells and enhance their sensitivity to apoptosis when induced by Apo2L/TRAIL through modification of O-glycans.