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Expression of a Core 3 Disialyl-Le(x) Hexasaccharide in Human Colorectal Cancers: A Potential Marker of Malignant Transformation in Colon.

Robbe-Masselot, Catherine; Herrmann, Annkatrin LU ; Maes, Emmanuel; Carlstedt, Ingemar LU ; Michalski, Jean-Claude and Capon, Calliope (2009) In Journal of Proteome Research
Abstract
Cancer-associated alterations in cell surface and secreted glycoproteins have been catalogued for many years but many of the studies of alterations in mucin carbohydrate have relied on histochemical or immunohistochemical methods, with little direct chemical analysis. In this study, we analyzed the O-glycosylation pattern of MUC2 glycoprotein isolated from colorectal carcinomas, transitional mucosa and resection margins from three patients with blood group A, B and O, respectively. After alkaline borohydride treatment, the released oligosaccharides were structurally characterized by nanoESI Q-TOF tandem mass spectrometry without prior fractionation or derivatization. As expected, we found an increased expression of sialyl-Tn antigen in the... (More)
Cancer-associated alterations in cell surface and secreted glycoproteins have been catalogued for many years but many of the studies of alterations in mucin carbohydrate have relied on histochemical or immunohistochemical methods, with little direct chemical analysis. In this study, we analyzed the O-glycosylation pattern of MUC2 glycoprotein isolated from colorectal carcinomas, transitional mucosa and resection margins from three patients with blood group A, B and O, respectively. After alkaline borohydride treatment, the released oligosaccharides were structurally characterized by nanoESI Q-TOF tandem mass spectrometry without prior fractionation or derivatization. As expected, we found an increased expression of sialyl-Tn antigen in the colonic cancer mucins. A more interesting feature was the increased expression of a core 3 sialyl-Le(x) hexasaccharide, NeuAcalpha2-3Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-3(NeuAcalpha2-6)GalNAc in tumor, which appeared to compete with its sulfo-Le(x) counterpart in normal tissue, SO3-3Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-3(NeuAcalpha2-6)GalNAc. This antigen, whose structure was confirmed by NMR experiments, is based on a core 3 glycan and may be a potential marker for the malignant transformation of colonic cells. Unexpectedly, most of the glycans recovered in normal and carcinomas extracts were based on a sialylated core 3, GlcNAcbeta1-3(NeuAcalpha2-6)GalNAcol. Moreover, the pattern of glycosylation was very similar between mucins isolated from each sample, the main differences related to the level of expression of the major oligosaccharides. The data obtained in this investigation may have value for future screening studies on colorectal cancer. (Less)
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Contribution to journal
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published
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in
Journal of Proteome Research
publisher
The American Chemical Society
external identifiers
  • pmid:19152289
  • scopus:61849112797
ISSN
1535-3893
DOI
10.1021/pr800740j
language
English
LU publication?
yes
id
f9e162ac-2939-4716-b5d1-3b3b517792b5 (old id 1289589)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19152289?dopt=Abstract
date added to LUP
2009-02-04 11:12:08
date last changed
2017-01-01 07:40:51
@article{f9e162ac-2939-4716-b5d1-3b3b517792b5,
  abstract     = {Cancer-associated alterations in cell surface and secreted glycoproteins have been catalogued for many years but many of the studies of alterations in mucin carbohydrate have relied on histochemical or immunohistochemical methods, with little direct chemical analysis. In this study, we analyzed the O-glycosylation pattern of MUC2 glycoprotein isolated from colorectal carcinomas, transitional mucosa and resection margins from three patients with blood group A, B and O, respectively. After alkaline borohydride treatment, the released oligosaccharides were structurally characterized by nanoESI Q-TOF tandem mass spectrometry without prior fractionation or derivatization. As expected, we found an increased expression of sialyl-Tn antigen in the colonic cancer mucins. A more interesting feature was the increased expression of a core 3 sialyl-Le(x) hexasaccharide, NeuAcalpha2-3Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-3(NeuAcalpha2-6)GalNAc in tumor, which appeared to compete with its sulfo-Le(x) counterpart in normal tissue, SO3-3Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-3(NeuAcalpha2-6)GalNAc. This antigen, whose structure was confirmed by NMR experiments, is based on a core 3 glycan and may be a potential marker for the malignant transformation of colonic cells. Unexpectedly, most of the glycans recovered in normal and carcinomas extracts were based on a sialylated core 3, GlcNAcbeta1-3(NeuAcalpha2-6)GalNAcol. Moreover, the pattern of glycosylation was very similar between mucins isolated from each sample, the main differences related to the level of expression of the major oligosaccharides. The data obtained in this investigation may have value for future screening studies on colorectal cancer.},
  author       = {Robbe-Masselot, Catherine and Herrmann, Annkatrin and Maes, Emmanuel and Carlstedt, Ingemar and Michalski, Jean-Claude and Capon, Calliope},
  issn         = {1535-3893},
  language     = {eng},
  month        = {01},
  publisher    = {The American Chemical Society},
  series       = {Journal of Proteome Research},
  title        = {Expression of a Core 3 Disialyl-Le(x) Hexasaccharide in Human Colorectal Cancers: A Potential Marker of Malignant Transformation in Colon.},
  url          = {http://dx.doi.org/10.1021/pr800740j},
  year         = {2009},
}