title: 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.
abstract: 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 A1[3]G(4)2S2-3. 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.
authors.affiliation: Institute of Zoology, Jagiellonian University, 9 Gronostajowa Street, Krakow, Poland. dorota.hoja-lukowicz@uj.edu.pl
authors.forename: Dorota
authors.initials: D
authors.lastname: Hoja-Łukowicz
authors.forename: Paweł
authors.initials: P
authors.lastname: Link-Lenczowski
authors.forename: Andrea
authors.initials: A
authors.lastname: Carpentieri
authors.forename: Angela
authors.initials: A
authors.lastname: Amoresano
authors.forename: Ewa
authors.initials: E
authors.lastname: Pocheć
authors.forename: Konstantin A
authors.initials: KA
authors.lastname: Artemenko
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergquist
authors.forename: Anna
authors.initials: A
authors.lastname: Lityńska
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry; D000606:Amino Sugars / Q000737:chemistry; D014408:Biomarkers, Tumor; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D000939:Epitopes / Q000737:chemistry; D005643:Fucose / Q000737:chemistry; D005690:Galactose / Q000737:chemistry*; D006801:Humans; D008545:Melanoma / Q000737:chemistry* / Q000473:pathology; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D009361:Neoplasm Invasiveness; D039842:Neural Cell Adhesion Molecule L1 / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry*
chemical_list: D000606:Amino Sugars; D014408:Biomarkers, Tumor; D000939:Epitopes; D039842:Neural Cell Adhesion Molecule L1; D011134:Polysaccharides; C032233:lactosamine; D005643:Fucose; D019158:N-Acetylneuraminic Acid; D000117:Acetylglucosamine; D005690:Galactose