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01-08-2007 | Original Article

The C-type lectin MGL expressed by dendritic cells detects glycan changes on MUC1 in colon carcinoma

Authors: Eirikur Saeland, Sandra J. van Vliet, Malin Bäckström, Venice C. M. van den Berg, Teunis B. H. Geijtenbeek, Gerrit A. Meijer, Yvette van Kooyk

Published in: Cancer Immunology, Immunotherapy | Issue 8/2007

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.

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Title: The C-type lectin MGL expressed by dendritic cells detects glycan changes on MUC1 in colon carcinoma
Authors: Eirikur Saeland
Sandra J. van Vliet
Malin Bäckström
Venice C. M. van den Berg
Teunis B. H. Geijtenbeek
Gerrit A. Meijer
Yvette van Kooyk
Publication date: 01-08-2007
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 8/2007
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-006-0274-z

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