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.