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Colorectal cancer cell lines show striking diversity of their O-glycome reflecting the cellular differentiation phenotype

Artikel i vetenskaplig tidskrift
Författare K. Madunic
T. Zhang
O. A. Mayboroda
S. Holst
K. Stavenhagen
Chunsheng Jin
Niclas G. Karlsson
G. S. M. Lageveen-Kammeijer
M. Wuhrer
Publicerad i Cellular and Molecular Life Sciences
Sidor 14
ISSN 1420-682X
Publiceringsår 2020
Publicerad vid Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
Sidor 14
Språk en
Länkar dx.doi.org/10.1007/s00018-020-03504...
Ämnesord O-Glycosylation, Glycomics, Cell lines, Colorectal cancer, Mass, spectrometry, Porous graphitized carbon liquid chromatography, consensus molecular subtypes, histo-blood group, colon-cancer, selectin, ligand, tn antigen, expression, glycosylation, mucin, carcinoma, glycans, Biochemistry & Molecular Biology, Cell Biology
Ämneskategorier Cellbiologi

Sammanfattning

Alterations in protein glycosylation in colorectal cancer (CRC) have been extensively studied using cell lines as models. However, little is known about their O-glycome and the differences in glycan biosynthesis in different cell types. To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed. The released O-glycans were analysed on porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization. Associations between the observed glycan phenotypes with previously reported cell line transcriptome signatures were examined by canonical correlation analysis. Striking differences are observed between the O-glycomes of 26 CRC cell lines. Unsupervized principal component analysis reveals a separation between well-differentiated colon-like and undifferentiated cell lines. Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated alpha 2,6-core sialylated glycans. Moreover, the expression of glycan signatures associates with the expression of glycosyltransferases that are involved in their biosynthesis, providing a deeper insight into the regulation of glycan biosynthesis in different cell types. This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.

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