Glycosylation of human fetal mucins: a similar repertoire of O-glycans along the intestinal tract.
Intestinal mucins are very high molecular weight glycoproteins secreted by goblet cells lining the crypt and the surface of the colonic mucosa. Profound alterations of mucin O-glycans are observed in diseases such as cancer and inflammation, modifying the function of the cell and its antigenic and adhesive properties. Based on immunohistochemical studies, certain cancer- and inflammation- associated glycans have been defined as oncofetal antigens. However, little or no chemical analysis has allowed the structural elucidation of O-glycans expressed on human fetal mucins. In this paper, mucins were isolated from different regions of the normal human intestine (ileum, right, transverse and left colon) of eight fetuses with A, B or O blood group. After alkaline borohydride treatment, the released oligosaccharides were investigated by nanoESI Q-TOF MS/MS (electrospray ionization quadrupole time-of-flight tandem mass spectrometry). More than 117 different glycans were identified, mainly based on core 2 structures. Some core 1, 3 and 4 oligosaccharides were also found. Most of the structures were acidic with NeuAc residues mainly alpha2-6 linked to the N-acetylgalactosaminitol and sulphate residues 3-linked to galactose or 6-linked to GlcNAc. In contrast to adult human intestinal mucins, Sda/Cad determinants were not expressed on fetal mucin O-glycans and the presence of an acidic gradient along the intestinal tract was not observed. Similar patterns of glycosylation were found in each part of the intestine and the level of expression of the major oligosaccharides was in the same order of magnitude. This study could help determining new oncofetal antigens, which can be exploited for the diagnosis or the treatment of intestinal diseases.
Robbe-Masselot
Catherine
C
Unité de Glycobiologie Structurale et Fonctionnelle, UMR CNRS/USTL 8576, IFR 147, Université des Sciences et Technologies de Lille, 59655, Villeneuve d'Ascq, Cedex, France. catherine.robbe@univ-lille1.fr
Maes
Emmanuel
E
Rousset
Monique
M
Michalski
Jean-Claude
JC
Capon
Calliope
C
D000328:Adult; D001789:Blood Group Antigens / Q000378:metabolism; D002240:Carbohydrate Sequence; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D006031:Glycosylation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009005:Monosaccharides / Q000737:chemistry; D009077:Mucins / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009844:Oligosaccharides / Q000737:chemistry / Q000302:isolation & purification; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization
D001789:Blood Group Antigens; D009005:Monosaccharides; D009077:Mucins; D009844:Oligosaccharides; D011134:Polysaccharides; D019158:N-Acetylneuraminic Acid