1. Major differences in glycosylation and fucosyltransferase expression in low-grade versus high-grade bladder cancer cell lines.
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Ezeabikwa, Bernadette, Mondal, Nandini, Antonopoulos, Aristotelis, Haslam, Stuart M, Matsumoto, Yasuyuki, Martin-Caraballo, Miguel, Lehoux, Sylvain, Mandalasi, Msano, Ishaque, Ali, Heimburg-Molinaro, Jamie, Cummings, Richard D, and Nyame, Anthony K
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BLADDER cancer ,CELL lines ,GENE expression profiling ,MEMBRANE glycoproteins ,GLYCAN structure ,GLYCANS - Abstract
Bladder cancer is the ninth most frequently diagnosed cancer worldwide, and there is a need to develop new biomarkers for staging and prognosis of this disease. Here we report that cell lines derived from low-grade and high-grade bladder cancers exhibit major differences in expression of glycans in surface glycoproteins. We analyzed protein glycosylation in three low-grade bladder cancer cell lines RT4 (grade-1-2), 5637 (grade-2), and SW780 (grade-1), and three high-grade bladder cancer cell lines J82COT (grade-3), T24 (grade-3) and TCCSUP (grade-4), with primary bladder epithelial cells, A/T/N, serving as a normal bladder cell control. Using a variety of approaches including flow cytometry, immunofluorescence, glycomics and gene expression analysis, we observed that the low-grade bladder cancer cell lines RT4, 5637 and SW780 express high levels of the fucosylated Lewis-X antigen (Lex, CD15) (Galβ1–4(Fucα1–3)GlcNAcβ1-R), while normal bladder epithelial A/T/N cells lack Le
x expression. T24 and TCCSUP cells also lack Lex , whereas J82COT cells express low levels of Lex . Glycomics analyses revealed other major differences in fucosylation and sialylation of N -glycans between these cell types. O -glycans are highly differentiated, as RT4 cells synthesize core 2-based O -glycans that are lacking in the T24 cells. These differences in glycan expression correlated with differences in RNA expression levels of their cognate glycosyltransferases, including α1–3/4-fucosyltransferase genes. These major differences in glycan structures and gene expression profiles between low- and high-grade bladder cancer cells suggest that glycans and glycosyltransferases are candidate biomarkers for grading bladder cancers. [ABSTRACT FROM AUTHOR]- Published
- 2021
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