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

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.

Abbreviations

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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Correspondence to Ninoslav Mitić.

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Mitić, N., Milutinović, B. & Janković, M. CA-125 of fetal origin can act as a ligand for dendritic cell-specific ICAM-3-grabbing non-integrin. Cell Mol Biol Lett 19, 249–261 (2014). https://doi.org/10.2478/s11658-014-0194-4

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Keywords

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