L1CAM from human melanoma carries a novel type of N-glycan with Galβ1-4Galβ1- motif: Involvement of N-linked glycans in migratory and invasive behaviour of melanoma cells
2013 (English)In: Glycoconjugate Journal, ISSN 0282-0080, E-ISSN 1573-4986, Vol. 30, no 3, 205-225 p.Article in journal (Refereed) Published
Dramatic changes in glycan biosynthesis during oncogenic transformation result in the emergence of marker glycans on the cell surface. We analysed the N- linked glycans of L1CAM from different stages of melanoma progression, using high-performance liquid chromatography combined with exoglycosidase sequencing, matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry, and lectin probes. L1CAM oligosaccharides are heavily sialylated, mainly digalactosylated, biantennary complex-type structures with galactose β1-4/3-linked to GlcNAc and with or without fucose α1-3/6-linked to GlcNAc. Hybrid, bisected hybrid, bisected triantennary and tetraantennary complex oligosaccharides, and β1-6-branched complex-type glycans with or without lactosamine extensions are expresses at lower abundance. We found that metastatic L1CAM possesses only α2-6-linked sialic acid and the loss of α2-3-linked sialic acid in L1CAM is a phenomenon observed during the transition of melanoma cells from VGP to a metastatic stage. Unexpectedly, we found a novel monoantennary complex-type oligosaccharide with a Galβ1-4Galβ1- epitope capped with sialic acid residues A1G(4)2S 2-3 . To our knowledge this is the first report documenting the presence of this oligosaccharide in human cancer. The novel and unique N- glycan should be recognised as a new class of human melanoma marker. In functional tests we demonstrated that the presence of cell surface α2-3-linked sialic acid facilitates the migratory behaviour and increases the invasiveness of primary melanoma cells, and it enhances the motility of metastatic cells. The presence of cell surface α2-6-linked sialic acid enhances the invasive potential of both primary and metastatic melanoma cells. Complex-type oligosaccharides in L1CAM enhance the invasiveness of metastatic melanoma cells.
Place, publisher, year, edition, pages
Springer Netherlands, 2013. Vol. 30, no 3, 205-225 p.
IdentifiersURN: urn:nbn:se:uu:diva-173876DOI: 10.1007/s10719-012-9374-5ISI: 000316750800002OAI: oai:DiVA.org:uu-173876DiVA: diva2:525479