Protein paucimannosylation, a type of truncated N-glycosylation with the simple composition Man(M)1-3GlcNAc2Fuc(F)0-1, was previously considered an invertebrate- and plant-specific glycoepitope absent in mammals. However, we recently established that protein paucimannosylation is a significant feature of the human innate immune system1. We have also made scattered encounters of paucimannosidic glycans in cancer cells and tissues, but it remains to be systematically investigated if paucimannosylation is a significant cancer glycoepitope. This glycomics-centric study investigates the association of protein paucimannosylation with a wide range of human cancer types and subtypes i.e. brain, breast, liver, colorectal, prostate, ovarian and acute promyelocytic leukemia and matching non-cancerous cultured cells and tissues by mapping the distribution of paucimannosidic N-glycans using porous graphitised carbon liquid chromatography tandem mass spectrometry. This N-glycomics strategy was able to accurately determine the total level of paucimannosidic glycans within the N-glycome and map the relative abundance of the individual paucimannosidic species including M2, M2F, M3 and M3F. The total level of paucimannosidic N-glycans varied dramatically across the cancer types (4-35%, n = 3 for all cancers), even within cancer sub-types as shown for the variation across six breast cancer subtypes (4-13%), but were in general higher than the paucimannosidic levels in non-cancerous cells (0-3%). The core fucosylated M2F and M3F were the predominant paucimannosidic N-glycans identified across the studied cancers and clear subcellular-specific differences were observed by the different levels of paucimannosylation in various protein extracts from the same cells. Based on these preliminary correlation-type observations, we conclude that protein paucimannosylation represents significant, but non-uniform glycoepitopes of human cancers. These findings advance our understanding of the glyco-features expressed by human cancers and promote further cause-effect type studies of paucimannosylation in tumorigenesis and metastasis.
1Thaysen-Andersen, Venkatakrishnan, Loke, Laurini, Diestel, Parker, Packer. J Biol Chem 2015, 290(14), 8789.