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Enzymatic basis for sialyl-Tn expression in human colon cancer cells

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Abstract

Sialyl-Tn antigen (SAα2-6 GalNAcα-Ser/Thr) is expressed as a cancer-associated antigen on the surface of cancer cells and its expression correlates with a poor prognosis in patients with colorectal and other adenocarcinomas. To understand the enzymatic basis of sialyl-Tn (STn) antigen expression, we used two clonal cell lines, LSB and LSC, derived from LS174T human colonic cancer cells. LSC cells express only the truncated carbohydrate antigen Tn (GalNAcα-Ser/Thr) and sialyl-Tn on their mucin molecules, whereas LSB cells express elongated oligosaccharide chains. Both cell lines demonstrated similar activities of glycosyltransferases involved in the biosynthesis of elongated and terminal structures of complex O-glycans. However, LSC cells were unable to synthesize core 1 (Galβ1-3GalNAc-) because the ubiquitous enzyme activity of UDP-Gal:GalNAc-R β3-Gal-transferase (core 1 β3-Gal-transferase) was lacking. Core 1 β3-Gal-transferase could not be reactivated in LSC cells by treatment with sodium butyrate or by in vivo growth of LSC cells in nude mice. In contrast, LSB cells were able to synthesize and process core 1 and core 2 (GlcNAcβ1-6 (Galβ1-3) GalNAc-). LSC cells represent the first example of a non-hematopoietic cell line which lacks core 1 β3-Gal-transferase activity. The lack of core 1 β3-Gal-transferase in LSC cells explains why they are incapable of forming the common mucin O-glycan core structures and are committed to synthesizing the short Tn and STn oligosaccharides. These findings suggest that the activity of core 1 β3-Gal-transferase is an important determinant of the STn phenotype of colon cancer cells.

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Authors and Affiliations

  1. Biochemistry Department, University of Toronto, Toronto, Ontario, Canada

    Inka Brockhausen & Nathalie Dickinson

  2. Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada

    Jimmy Yang

  3. Gastrointestinal Research Laboratory, The Mount Sinai School of Medicine, New York, USA

    Shunichiro Ogata & Steven H Itzkowitz

Authors
  1. Inka Brockhausen
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  2. Jimmy Yang
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  3. Nathalie Dickinson
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  4. Shunichiro Ogata
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  5. Steven H Itzkowitz
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Brockhausen, I., Yang, J., Dickinson, N. et al. Enzymatic basis for sialyl-Tn expression in human colon cancer cells. Glycoconj J 15, 595–603 (1998). https://doi.org/10.1023/A:1006967910803

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