title: Differential glycosylation of MUC1 and CEACAM5 between normal mucosa and tumour tissue of colon cancer patients.
abstract: Altered glycosylation in epithelial cancers may play an important role in tumour progression, as it may affect tumour cell migration and antigen presentation by antigen presenting cells. We specifically characterise the glycosylation patterns of two tumour antigens that are highly expressed in cancer tissue and often detected in their secreted form in serum: the epithelial mucin MUC1 and carcinoembryonic antigen (CEA, also called CEACAM5). We analysed 48 colorectal cancer patients, comparing normal colon and tumour epithelium within each patient. Lectin binding was studied by a standardised CEA/MUC1 capture ELISA, using several plant lectins, and the human C-type lectins MGL and DC-SIGN, and Galectin-3. Peanut agglutinin (PNA) bound to MUC1 from tumour tissue in particular, suggests increased expression of the Thomsen-Friedenreich antigen (TF-antigen) (Core 1, Galβ1-3GalNAc-Ser/Thr). Only small amounts of Tn-antigen (GalNAcα-Ser/Thr) expression was observed, but the human C-type lectin MGL showed increased binding to tumour-associated MUC1. Furthermore, sialylation was greatly enhanced. In sharp contrast, tumour-associated CEA (CEACAM5) contained high levels of the blood-group related carbohydrates, Lewis X and Lewis Y. This correlated strongly with the interaction of the human C-type lectin DC-SIGN to tumour-associated CEA, suggesting that CEA can be recognized and taken up by antigen presenting cells. In addition, increased mannose expression was observed and branched N-glycans were prominent, and this correlated well with human Galectin-3 binding. These data demonstrate that individual tumour antigens contain distinct glycan structures associated with cancer and, since glycans affect cellular interactions with its microenvironment, this may have consequences for progression of the disease.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Eirikur
authors.initials: E
authors.lastname: Saeland
authors.forename: Ana I
authors.initials: AI
authors.lastname: Belo
authors.forename: Sandra
authors.initials: S
authors.lastname: Mongera
authors.forename: Irma
authors.initials: I
authors.lastname: van Die
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000096:biosynthesis / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D058851:GPI-Linked Proteins / Q000378:metabolism; D037502:Galectin 3 / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism; D007983:Lewis Blood Group Antigens / Q000096:biosynthesis; D016256:Lewis X Antigen / Q000096:biosynthesis; D008358:Mannose / Q000096:biosynthesis; D018396:Mucin-1 / Q000378:metabolism*; D019887:Peanut Agglutinin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D037502:Galectin 3; D037181:Lectins, C-Type; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D008358:Mannose; D018396:Mucin-1; D019887:Peanut Agglutinin; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C527875:CEACAM5 protein, human; C094162:Lewis Y antigen; C506225:MGL lectin, human; C060192:MUC1 protein, human; C040286:Tn antigen; C016467:Thomsen-Friedenreich antigen