title: Expression of a core 3 disialyl-Le(x) hexasaccharide in human colorectal cancers: a potential marker of malignant transformation in colon.
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.
authors.affiliation: Unite de Glycobiologie Structurale et Fonctionnelle, Universite des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France. catherine.robbe@univ-lille1.fr
authors.forename: Catherine
authors.initials: C
authors.lastname: Robbe-Masselot
authors.forename: Annkatrin
authors.initials: A
authors.lastname: Herrmann
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Maes
authors.forename: Ingemar
authors.initials: I
authors.lastname: Carlstedt
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Michalski
authors.forename: Calliope
authors.initials: C
authors.lastname: Capon
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000378:metabolism; D001789:Blood Group Antigens / Q000737:chemistry / Q000378:metabolism; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002471:Cell Transformation, Neoplastic; D003106:Colon / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000473:pathology; D006801:Humans; D007983:Lewis Blood Group Antigens; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D055262:Mucin-2 / Q000737:chemistry / Q000378:metabolism; D009077:Mucins / Q000737:chemistry; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D001789:Blood Group Antigens; D007983:Lewis Blood Group Antigens; C494219:Lewis a oligosaccharide; C524625:MUC2 protein, human; D055262:Mucin-2; D009077:Mucins; D009844:Oligosaccharides