Abstract: P-glycoprotein (P-gp) overexpression is the most frequently observed cause of multidrug resistance in neoplastic cells. In our experiments, P-gp was expressed in L1210 mice leukemia cells (S cells) by selection with vincristine (R cells) or transfection with the gene encoding human P-gp (T cells). Remodeling of cell surface sugars is associated with P-gp expression in L1210 cells as a secondary cellular response. In this study, we monitored the alteration of cell surface saccharides by Sambucus nigra agglutinin (SNA), wheat germ agglutinin (WGA) and Maackia amurensis agglutinin (MAA). Sialic acid is predominantly linked to the surface of S, R and T cells via α-2,6 branched sugars that tightly bind SNA. The presence of sialic acid linked to the cell surface via α-2,3 branched sugars was negligible, and the binding of MAA (recognizing this branch) was much less pronounced than SNA. WGA induced greater cell death than SNA, which was bound to the cell surface and agglutinated all three L1210 cell-variants more effectively than WGA. Thus, the ability of lectins to induce cell death did not correlate with their binding efficiency and agglutination potency. Compared to S cells, P-gp positive R and T cells contain a higher amount of N-acetyl-glucosamine on their cell surface, which is associated with improved WGA binding. Both P-gp positive variants of L1210 cells are strongly resistant to vincristine as P-gp prototypical drug. This resistance could not be altered by liberalization of terminal sialyl residues from the cell surface by sialidase.
Keywords: L1210 cells; P-glycoprotein; cell surface sugars; Sambucus nigra agglutinin; wheat germ agglutinin; Maackia amurensis agglutinin; sialic acid; vincristine
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Bubencíkova, T.; Cholujová, D.; Messingerová, L.; Mislovicova, D.; Seres, M.; Breier, A.; Sulova, Z. Detection of Glycomic Alterations Induced by Overexpression of P-Glycoprotein on the Surfaces of L1210 Cells Using Sialic Acid Binding Lectins. Int. J. Mol. Sci. 2012, 13, 15177-15192.
Bubencíkova T, Cholujová D, Messingerová L, Mislovicova D, Seres M, Breier A, Sulova Z. Detection of Glycomic Alterations Induced by Overexpression of P-Glycoprotein on the Surfaces of L1210 Cells Using Sialic Acid Binding Lectins. International Journal of Molecular Sciences. 2012; 13(11):15177-15192.
Bubencíkova, Tatiana; Cholujová, Dana; Messingerová, Lucia; Mislovicova, Danica; Seres, Mario; Breier, Albert; Sulova, Zdena. 2012. "Detection of Glycomic Alterations Induced by Overexpression of P-Glycoprotein on the Surfaces of L1210 Cells Using Sialic Acid Binding Lectins." Int. J. Mol. Sci. 13, no. 11: 15177-15192.