title: Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) recognizes a novel ligand, Mac-2-binding protein, characteristically expressed on human colorectal carcinomas.
abstract: Dendritic cell (DC)-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is a type II transmembrane C-type lectin expressed on DCs such as myeloid DCs and monocyte-derived DCs (MoDCs). Recently, we have reported that DC-SIGN interacts with carcinoembryonic antigen (CEA) expressed on colorectal carcinoma cells. CEA is one of the most widely used tumor markers for gastrointestinal cancers such as colorectal cancer. On the other hand, other groups have reported that the level of Mac-2-binding protein (Mac-2BP) increases in patients with pancreatic, breast, and lung cancers, virus infections such as human immunodeficiency virus and hepatitis C virus, and autoimmune diseases. Here, we first identified Mac-2BP expressed on several colorectal carcinoma cell lines as a novel DC-SIGN ligand through affinity chromatography and mass spectrometry. Interestingly, we found that DC-SIGN selectively recognizes Mac-2BP derived from some colorectal carcinomas but not from the other ones. Furthermore, we found that the α1-3,4-fucose moieties of Le glycans expressed on DC-SIGN-binding Mac-2BP were important for recognition. DC-SIGN-dependent cellular interactions between immature MoDCs and colorectal carcinoma cells significantly inhibited MoDC functional maturation, suggesting that Mac-2BP may provide a tolerogenic microenvironment for colorectal carcinoma cells through DC-SIGN-dependent recognition. Importantly, Mac-2BP was detected as a predominant DC-SIGN ligand expressed on some primary colorectal cancer tissues from certain parts of patients in comparison with CEA from other parts, suggesting that DC-SIGN-binding Mac-2BP bearing tumor-associated Le glycans may become a novel potential colorectal cancer biomarker for some patients instead of CEA.
authors.affiliation: Research Center for Glycobiotechnology, Ritsumeikan University, Shiga 525-0058, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Nonaka
authors.forename: Bruce Yong
authors.initials: BY
authors.lastname: Ma
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Imaeda
authors.forename: Keiko
authors.initials: K
authors.lastname: Kawabe
authors.forename: Nobuko
authors.initials: N
authors.lastname: Kawasaki
authors.forename: Keiko
authors.initials: K
authors.lastname: Hodohara
authors.forename: Nana
authors.initials: N
authors.lastname: Kawasaki
authors.forename: Akira
authors.initials: A
authors.lastname: Andoh
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujiyama
authors.forename: Toshisuke
authors.initials: T
authors.lastname: Kawasaki
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C114782:TAA90K protein, human