Single molecule study of heterotypic interactions between mucins possessing the Tn cancer antigen

Kristin E. Haugstad, Bjørn T. Stokke, C. Fred Brewer, Thomas A. Gerken, Marit Sletmoen

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Mucins are linear, heavily O-glycosylated proteins with physiological roles that include cell signaling, cell adhesion, inflammation, immune response and tumorgenesis. Cancer-associated mucins often differ from normal mucins by presenting truncated carbohydrate chains. Characterization of the binding properties of mucins with truncated carbohydrate side chains could thus prove relevant for understanding their role in cancer mechanisms such as metastasis and recognition by the immune system. In this work, heterotypic interactions of model mucins that possess the Tn (GalNA-cαThr/Ser) and T (Galβ1-3GalNAcαThr/Ser) cancer antigens derived from porcine submaxillary mucin (PSM) were studied using atomic force microscopy. PSM possessing only the Tn antigen (Tn-PSM) was found to bind to PSM analogs possessing a combination of T, Tn and STn antigens as well as biosynthetic analogs of the core 1 blood group A tetrasaccharide (GalNAcα1-3[Fucα1-2] Galβ1-3GalNAcαSer/Thr). The rupture forces for the heterotypic interactions ranged from 18- to 31 pN at a force-loading rate of ∼0.5 nN/s. The thermally averaged distance from the bound complex to the transition state (χβ) was estimated to be in the range 0.37-0.87 nm for the first barrier of the Bell Evans analysis and within 0.34-0.64 nm based on a lifetime analysis. These findings reveal that the binding strength and energy landscape for heterotypic interactions of Tn-PSM with the above mucins, resemble homotypic interactions of Tn-PSM. This suggests common carbohydrate epitope interactions for the Tn cancer antigen with the above mucin analogs, a finding that may be important to the role of the Tn antigen in cancer cells.

Original languageEnglish (US)
Pages (from-to)524-534
Number of pages11
JournalGlycobiology
Volume25
Issue number5
DOIs
StatePublished - Jan 1 2015

Keywords

  • AFM
  • Carbohydrate
  • Dynamic force spectroscopy
  • Glycan
  • Interactions
  • STn-antigen
  • Tn-antigen

ASJC Scopus subject areas

  • Biochemistry

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