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.