Globo H ceramide (Globo H)

Globo H ceramide is a hexasaccharide glycosphingolipid with the structure Fucα(1-2)Galβ(1-3)GalNAcβ(1-3)Galα(1-4)Galβ(1-4)Glcβ(1) linked to ceramide, originally identified on breast cancer cell line MCF-7 and recognized by monoclonal antibody MBr1. It belongs to the globo-series glycosphingolipids, biosynthesized via enzymes like β1,3-galactosyltransferase 5 (B3GALT5) and fucosyltransferase 2 (FUT2), which are upregulated in tumors. Absent in normal tissues like liver, Globo H ceramide is highly expressed on cancer cell surfaces in breast, prostate, lung, and intrahepatic cholangiocarcinoma (ICC), where it correlates with aggressive features such as vascular invasion, relapse, and reduced survival (e.g., 41% ICC positivity linked to shorter RFS and OS). Functionally, it drives tumor progression by promoting angiogenesis through endothelial uptake and phospholipase Cβ1 activation, and induces immunosuppression via lymphocyte incorporation, downregulating Notch1 signaling and T-cell activation. As a promising theranostic tumor-associated carbohydrate antigen, it serves as a prognostic biomarker in ICC but lacks approved interacting drugs, with research focusing on vaccine conjugates and analogs for cancer immunotherapy.

Other names

Globo HGHCer