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. 2014 Apr 24;19(2):249–261. doi: 10.2478/s11658-014-0194-4

CA-125 of fetal origin can act as a ligand for dendritic cell-specific ICAM-3-grabbing non-integrin

Ninoslav Mitić 1,✉, Bojana Milutinović 1, Miroslava Janković 1
PMCID: PMC6275607  PMID: 24764143

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.

Keywords: CA-125, Mucin 16, DC-SIGN, C-type lectin, Carbohydrate binding, Pathogen-related glycoconjugates, Mannan, Helicobacter pylori

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Abbreviations used

afCA-125

CA-125 from amniotic fluid

CA-125

coelomicepithelium related antigen

clCA-125

CA-125 from ovarian carcinoma OVCAR-3 cell line

ConA

concanavalin A

DC-SIGN

dendritic cell-specific ICAM-3-grabbing nonintegrin

hu-FEDS

human fetoembryonic defense system

Lex

Lewisx antigen

Ley

Lewisy antigen

MUC16

mucin 16

pCA-125

pregnancy-associated cancer antigen 125

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