Enhanced self-association of mucins possessing the T and Tn carbohydrate cancer antigens at the single-molecule level.

摘要: 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) Tn (GalNAcαThr/Ser) cancer antigens, which diagnostic markers for several cancers, including colon cancer. We have used AFM based single-molecule forced unbinding under near physiological conditions to investigate self-interactions between porcine submaxillary mucin (PSM) as well PSM analogs possessing various carbohydrates T- Tn-antigen. Distributions forces corresponding force loading rates were determined from 0.18 nN/s 39 nN/s, processed yield most probable f* lifetimes interactions. Parameter varied range 27 50 pN at about 2 among mucins. All samples investigated showed self-interaction, but tendency was greatest displaying only Tn-antigen (Tn-PSM) or a mixture Tn-, T-antigen, trisaccharide Fucα1,2Galβ1,3GalNAc (Tri-PSM). Weaker observed native (Fd-PSM), consists nearly equal longer core 1 blood group A tetrasaccharide (GalNAcα1,3(Fucα1,2)Galβ1,3GalNAcαSer/Thr) The data consistent with truncated glycans enhancing self-interaction These carbohydrate antigens may, thus, play an active role disease by constitutively activating mucin-type receptors self-association on cells.