Abstract
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, cancerderived 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.
Original language | English (US) |
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Pages (from-to) | 249-261 |
Number of pages | 13 |
Journal | Cellular and Molecular Biology Letters |
Volume | 19 |
Issue number | 2 |
DOIs | |
State | Published - Jun 2014 |
Externally published | Yes |
Keywords
- C-type lectin
- CA-125
- Carbohydrate binding
- DC-SIGN
- Helicobacter pylori
- Mannan
- Mucin 16
- Pathogen-related glycoconjugates
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology