Terminal β-galactose–containing O-linked glycans (O-Gal glycans)

Terminal β-galactose–containing O-linked glycans are carbohydrate structures covalently attached to the hydroxyl group of serine or threonine residues on cell-surface proteins. These glycans, most notably the Thomsen-Friedenreich (TF) antigen (Galβ1-3GalNAcα1-O-Ser/Thr), serve as critical ligands for endogenous lectins such as galectins and selectins (Springer, 1984, Science). In healthy tissues, these terminal galactose residues are typically masked by sialic acid; however, in many adenocarcinomas, they become exposed or overexpressed due to altered glycosyltransferase activity, facilitating tumor cell adhesion, migration, and immune evasion (Heimburg-Molinaro et al., 2011, Cancer Letters). This exposure allows cancer cells to interact with galectins on endothelial and immune cells, promoting metastasis and suppressing anti-tumor immune responses (Liu & Rabinovich, 2005, Nature Reviews Cancer). Consequently, these glycans are significant targets for the development of diagnostic biomarkers and therapeutic agents, including monoclonal antibodies like JAA-F11 and small-molecule galectin inhibitors. Targeting the galectin-glycan lattice aims to disrupt the pro-tumorigenic microenvironment and restore effective immune surveillance (Johannes et al., 2018, Journal of Cell Science).

Other names

Thomsen-Friedenreich antigenTF antigenT antigenGal-terminated O-glycansCore 1 O-glycansGalβ1-3GalNAcα1-Ser/Thr

Competitive inhibition of galectin-glycan binding, induction of antibody-dependent cellular cytotoxicity (ADCC), and blockade of tumor cell adhesion to the vascular endothelium.