CA-125 of fetal origin can act as a ligand for dendritic cell-specific ICAM-3-grabbing non-integrin.
CA-125 (coelomic epithelium-related antigen) forms the extracellular portion of transmembrane mucin 16 (MUC16). It is shed after proteolytic degradation. Due to structural heterogeneity, CA-125 ligand capacity and biological roles are not yet understood. In this study, we assessed CA-125 as a ligand for dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN), which is a C-type lectin showing specificity for mannosylated and fucosylated structures. It plays a role as a pattern recognition molecule for viral and bacterial glycans or as an adhesion receptor. We probed a human DC-SIGN-Fc chimera with CA-125 of fetal or cancer origin using solid- or fluid-phase binding and inhibition assays. The results showed that DC-SIGN binds to CA-125 of fetal origin and that this interaction is carbohydrate-dependent. By contrast, cancer-derived CA-125 displayed negligible binding. Inhibition assays indicated differences in the potency of CA-125 to interfere with DC-SIGN binding to pathogen-related glycoconjugates, such as mannan and Helicobacter pylori antigens. The differences in ligand properties between CA-125 of fetal and cancer origin may be due to specificities of glycosylation. This might influence various functions of dendritic cells based on their subset diversity and maturation-related functional capacity.
Institute for the Application of Nuclear Energy, INEP, Department for Immunochemistry and Glycobiology, University of Belgrade, Banatska 31b, 11080, Zemun, Serbia, ninoslavm@inep.co.rs.
Ninoslav
N
Mitić
Bojana
B
Milutinović
Miroslava
M
Janković
D018394:CA-125 Antigen / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005333:Fetus / Q000378:metabolism*; D006001:Glycoconjugates / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry / Q000378:metabolism; D037181:Lectins, C-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D018394:CA-125 Antigen; D015815:Cell Adhesion Molecules; D006001:Glycoconjugates; D055767:Immobilized Proteins; D037181:Lectins, C-Type; D008024:Ligands; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin