title: The C-type lectin MGL expressed by dendritic cells detects glycan changes on MUC1 in colon carcinoma.
abstract: The epithelial mucin MUC1 is a high molecular weight membrane glycoprotein frequently overexpressed and aberrantly glycosylated in adenocarcinoma. Mucins normally contain high amounts of O-linked carbohydrate structures that may influence immune reactions to this antigen. During malignant transformation, certain glyco-epitopes of MUC1, such as Tn-antigen, TF-antigen and their sialylated forms become exposed. The role of these glycan structures in tumor biology is unknown, but their presence is known to correlate with poor prognosis in several adenocarcinomas. We analyzed the potency of MUC1 containing Tn-antigens (MUC1-Tn) to target C-type lectins that function as carbohydrate recognition and uptake molecules on dendritic cells (DC). We identified the macrophage galactose type C-type lectin (MGL), expressed by both DC and macrophages, as the receptor for recognition and binding of MUC1-Tn. To validate the occurrence of MGL-MUC1 interactions in situ, we studied the binding of MGL to MUC1 in primary colon carcinoma tissue. Isolation of MUC1 out of colon carcinoma tissue showed strong binding activity to MGL. Interestingly, MGL binding to MUC1 was highly correlated to binding by the lectin Helix pomatia agglutinin (HPA), which is associated with poor prognosis in colorectal cancer. The detection of MGL positive cells in situ at the tumor site together with the modified glycosylation status of MUC1 to target MGL on DC suggests that MGL positive antigen presenting cells may play a role in tumor progression.
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: Sandra J
authors.initials: SJ
authors.lastname: van Vliet
authors.forename: Malin
authors.initials: M
authors.lastname: Bäckström
authors.forename: Venice C M
authors.initials: VC
authors.lastname: van den Berg
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
mesh_terms: D000116:Acetylgalactosamine / Q000494:pharmacology; D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology / Q000378:metabolism*; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D003106:Colon / Q000737:chemistry / Q000166:cytology; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D004705:Endocytosis; D005260:Female; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007413:Intestinal Mucosa / Q000737:chemistry / Q000166:cytology; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000166:cytology; D009005:Monosaccharides / Q000494:pharmacology; D018396:Mucin-1; D009077:Mucins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology; D020080:Tandem Repeat Sequences; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000116:Acetylgalactosamine; D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D015815:Cell Adhesion Molecules; D007074:Immunoglobulin G; D037181:Lectins, C-Type; D009005:Monosaccharides; D018396:Mucin-1; D009077:Mucins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C506225:MGL lectin, human; C060192:MUC1 protein, human; C040286:Tn antigen