Sialic Acid Modification Of The Stem Cell Markers Cd133 And Function

Sialylation of CD133 contributes its stability in cells.CD133(prominin-1), a member of five transmembrane glycoprotein Prominin family, In mammals, CD133 is expressed in various embryonic and adult epithelial cells, as well as in nonepithelial cells, such as hematopoietic stem cells. In recent years, CD133 has been found specially expressed in a subpopulation of tumor cells which is responsible of initiating, maintaining, metastasis and recurrence of cancer (cancer stem cells) in a serial of human tumors. Therefore, CD133 has been widely used to identify and isolate cancer stem cells for further eradication of these novel cancer cells. However, the biological function of CD133 is still unknown and some studies suggest that the role of CD133 as a cancer stem cell marker may have some sort correlation with its glycosylation pattern.Sialylation is a frequently occurring terminal modification to glycan of glycoprotein. Sialylation is involved in multiple biological process, including virus infection, cell-cell interaction, tumor metastasis and regulating protein stability.In our study we found that cancer stem cell marker CD133 posses terminal sialylation which in turn contributes its stability in cells. We first treated CD133 endogenously expressed in neural stem cells and glioma-initiating cell with neuraminidase and found that CD133 showed a decrease in molecular weight. CD133 stably expressed in malignant glioblastoma cell line U87MG also showed a decreased molecular weight after neuraminidase treatment, suggesting a sialylation modification to CD133. Then we confirmed that sialyl residues were linked to CD133 N-glycan through a a 2,3-linkage. Furthermore, we found that CD133 was degraded by lysosome in cells and desialylation of CD133 facilated its degredation by lysosome.Taken together, the stem cell marker CD133 could be sialylated at its N-glycan terminal, and terminal sialylation facilitated CD133 stability, enhance our understanding of the utility of glycosylated CD133 epitopes in defining neural stem cells and tumor-initiating cells.