Enhanced self-association of mucins possessing the T and Tn carbohydrate cancer antigens at the single-molecule level
Document Type
Article
Publication Date
5-14-2012
Abstract
Mucins are linear O-glycosylated glycoproteins involved in inflammation, cell adhesion, and tumorigenesis. Cancer-associated mucins often possess increased expression of the T (Galβ1,3GalNAcαThr/Ser) and Tn (GalNAcαThr/Ser) cancer antigens, which are diagnostic markers for several cancers, including colon cancer. We have used AFM based single-molecule forced unbinding under near physiological conditions to investigate the self-interactions between porcine submaxillary mucin (PSM) as well as between PSM analogs possessing various carbohydrates including the T- and Tn-antigen. Distributions of unbinding forces and corresponding force loading rates were determined for force loading rates from 0.18 nN/s to 39 nN/s, and processed to yield most probable unbinding forces f* and lifetimes of the interactions. Parameter f* varied in the range 27 to 50 pN at force loading rates of about 2 nN/s among the various mucins. All mucin samples investigated showed self-interaction, but the tendency was greatest for PSM displaying only the Tn-antigen (Tn-PSM) or a mixture of Tn-, T-antigen, and the trisaccharide Fucα1,2Galβ1,3GalNAc (Tri-PSM). Weaker self-interactions were observed for native PSM (Fd-PSM), which consists of a nearly equal mixture of the longer core 1 blood group A tetrasaccharide (GalNAcα1,3(Fucα1,2) Galβ1,3GalNAcαSer/Thr) and Tn-antigen. The data are consistent with the truncated Tn and T glycans enhancing self-interaction of the mucins. These carbohydrate cancer antigens may, thus, play an active role in the disease by constitutively activating mucin and mucin-type receptors by self-association on cells. © 2012 American Chemical Society.
Publication Title
Biomacromolecules
Recommended Citation
Haugstad, K.,
Gerken, T.,
Stokke, B.,
Dam, T.,
Brewer, C.,
&
Sletmoen, M.
(2012).
Enhanced self-association of mucins possessing the T and Tn carbohydrate cancer antigens at the single-molecule level.
Biomacromolecules,
13(5), 1400-1409.
http://doi.org/10.1021/bm300135h
Retrieved from: https://digitalcommons.mtu.edu/michigantech-p/7881