TY - JOUR
T1 - Targeting alpha2,3-sialylated glycan in glioma stem-like cells by Maackia amurensis lectin-II
T2 - A promising strategy for glioma treatment
AU - Putthisen, Siyaporn
AU - Silsirivanit, Atit
AU - Panawan, Orasa
AU - Niibori-Nambu, Akiko
AU - Nishiyama-Ikeda, Yuki
AU - Ma-In, Prasertsri
AU - Luang, Sukanya
AU - Ohta, Kunimasa
AU - Muisuk, Kanha
AU - Wongkham, Sopit
AU - Araki, Norie
N1 - Funding Information:
Research grants from the Japan Society for the Promotion of Science (JSPS) to A.S. and N.A. ( 14F04099 ); from MEXT / JSPS KAKENHI to N.A. ( 19H03772 ) and to N.A. and A.NN. (17K07199); from the Mekong Health Science Research Institute , Khon Kaen University to A.S. (12/2561), from Faculty of Medicine , Khon Kaen University to S.P. and A.S·( IN63236 ).
Funding Information:
We would like to thank the supports from the Japan Society for the Promotion of Science (JSPS) to A.S. and N.A. ( P14099R , 14F04099 ), research grants from MEXT / JSPS KAKENHI to N.A. ( 19H03772 ), to N.A. and A.NN. (17K07199), the Mekong Health Science Research Institute to A.S. (12/2561), Faculty of Medicine to S.P. and A.S. ( IN63236 ), Khon Kaen University , Khon Kaen, Thailand. Thanks, Prof. Yukifumi Nawa, for English editing via the Publication Clinic of Khon Kaen University.
Funding Information:
Research grants from the Japan Society for the Promotion of Science (JSPS) to A.S. and N.A. (14F04099); from MEXT/JSPS KAKENHI to N.A. (19H03772) and to N.A. and A.NN. (17K07199); from the Mekong Health Science Research Institute, Khon Kaen University to A.S. (12/2561), from Faculty of Medicine, Khon Kaen University to S.P. and A.S·(IN63236).We would like to thank the supports from the Japan Society for the Promotion of Science (JSPS) to A.S. and N.A. (P14099R, 14F04099), research grants from MEXT/JSPS KAKENHI to N.A. (19H03772), to N.A. and A.NN. (17K07199), the Mekong Health Science Research Institute to A.S. (12/2561), Faculty of Medicine to S.P. and A.S. (IN63236), Khon Kaen University, Khon Kaen, Thailand. Thanks, Prof. Yukifumi Nawa, for English editing via the Publication Clinic of Khon Kaen University.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.yexcr.2021.112949
DO - 10.1016/j.yexcr.2021.112949
M3 - Article
C2 - 34843714
AN - SCOPUS:85120174722
SN - 0014-4827
VL - 410
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
M1 - 112949
ER -