High-mannose N-glycan (HM-N-glycan)

High-mannose N-glycans are a class of N-linked oligosaccharides characterized by a high number of mannose residues attached to a core pentasaccharide. In healthy cells, these glycans are typically transient intermediates in the endoplasmic reticulum (ER) and are processed into complex or hybrid types before reaching the cell surface (12, 15). However, in various cancers, including bladder cancer, there is an aberrant accumulation and presentation of high-mannose glycans on the cell surface glycoproteins, a phenomenon often termed hypermannosylation (7, 12). This shift is frequently driven by the downregulation of mannosidases or the upregulation of mannosyltransferases such as ALG3 (1, 18). These surface glycans serve as specific docking sites for mannose-binding proteins, such as the FimH adhesin of uropathogenic E. coli and various plant lectins like Concanavalin A (7, 11). This unique presentation is being exploited for targeted therapies, including recombinant BCG strains and lectin-drug conjugates (LDCs), which aim to enhance the efficacy and reduce the toxicity of intravesical treatments for non-muscle invasive bladder cancer (NMIBC) (2, 10, 11).

Other names

Oligomannose-type N-glycanHigh-mannose glycanMannose-rich glycanOligomannoseHM-glycan

Lectin-mediated drug delivery, Enhanced bacterial attachment and internalization, Immune response activation, Competitive binding to mannose-binding receptors