Major differences in glycosylation and fucosyltransferase expression in low-grade versus high-grade bladder cancer cell lines. (5th August 2021)

• Record Type: Journal Article
• Authors: 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; Nyame, Anthony K
• Is Part Of: Glycobiology. Volume 31:Number 11(2021)
• Page Start: 1444
• Page End: 1463
• Publication Date: 2021-08-05
• Subjects: bladder cancer -- fucosyltransferase -- glycan marker -- glycomics -- Lewis-X; Glycoproteins -- Periodicals; Glycolipids -- Periodicals; Glycoconjugates -- Periodicals; 572.567
• DOI: 10.1093/glycob/cwab083
• Languages: English
• ISSNs: 0959-6658

Abstract

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 Le x, whereas J82COT cells express low levels of Le x . 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.