TY - JOUR
T1 - The C-type lectin MGL expressed by dendritic cells detects glycan changes on MUC1 in colon carcinoma
AU - Saeland, Eirikur
AU - van Vliet, Sandra J
AU - Bäckström, Malin
AU - van den Berg, Venice C M
AU - Geijtenbeek, Teunis B H
AU - Meijer, Gerrit A
AU - van Kooyk, Yvette
PY - 2007/8
Y1 - 2007/8
N2 - 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.
AB - 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.
KW - Acetylgalactosamine/pharmacology
KW - Adenocarcinoma/immunology
KW - Animals
KW - Antigens, Neoplasm/immunology
KW - Antigens, Tumor-Associated, Carbohydrate/immunology
KW - CHO Cells
KW - Cell Adhesion Molecules/immunology
KW - Colon/chemistry
KW - Colonic Neoplasms/immunology
KW - Cricetinae
KW - Cricetulus
KW - Dendritic Cells/immunology
KW - Endocytosis
KW - Female
KW - Glycosylation
KW - Humans
KW - Immunoglobulin G/immunology
KW - Intestinal Mucosa/chemistry
KW - Lectins, C-Type/immunology
KW - Mice
KW - Mice, Inbred BALB C
KW - Monocytes/cytology
KW - Monosaccharides/pharmacology
KW - Mucin-1
KW - Mucins/immunology
KW - Neoplasm Proteins/immunology
KW - Protein Binding/drug effects
KW - Protein Processing, Post-Translational
KW - Protein Structure, Tertiary
KW - Receptors, Cell Surface/immunology
KW - Recombinant Fusion Proteins/chemistry
KW - Tandem Repeat Sequences
U2 - 10.1007/s00262-006-0274-z
DO - 10.1007/s00262-006-0274-z
M3 - Article
C2 - 17195076
VL - 56
SP - 1225
EP - 1236
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
SN - 0340-7004
IS - 8
ER -