Targeting alpha2,3-sialylated glycan in glioma stem-like cells by Maackia amurensis lectin-II: A promising strategy for glioma treatment.

Glioma stem/initiating cells have been considered a major cause of tumor recurrence and therapeutic resistance. In this study, we have established a new glioma stem-like cell (GSC), named U373-GSC, from the U373 glioma cell line. The cells exhibited stemness properties, e.g., expression of stem cell markers, self-renewal activity, multi-lineage differentiating abilities, and drug resistance. Using U373-GSC and GSC-03A-a GSC clone previously established from patient tissue, we have identified a novel GSC-associated sialic acid-modified glycan commonly expressed in both cell lines. Lectin fluorescence staining showed that Maackia amurensis lectin II (MAL-II)-binding alpha2,3-sialylated glycan (MAL-SG) was highly expressed in GSCs, and drastically decreased during FBS induced differentiation to glioma cells or little in the parental cells. Treatment of GSCs by MAL-II, compared with other lectins, showed that MAL-II significantly suppresses cell viability and sphere formation via induction of cell cycle arrest and apoptosis of the GSCs. Similar effects were observed when the cells were treated with a sialyltransferase inhibitor or sialidase. Taken together, we demonstrate for the first time that MAL-SGs/alpha-2,3 sialylations are upregulated and control survival/maintenances of GSCs, and their functional inhibitions lead to apoptosis of GSCs. MAL-SG could be a potential marker and therapeutic target of GSCs; its inhibitors, such as MAL-II, may be useful for glioma treatment in the future.