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.Electronic supplementary materialThe online version of this article (doi:10.1007/s10719-012-9374-5) contains supplementary material, which is available to authorized users.
Highlights
Alterations of the cell surface carbohydrate structures of cancer cells are suggested to affect normal cellular interactions and have been shown to facilitate tumour cell colonisation and metastasis
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 vertical growth phase (VGP) to a metastatic stage
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
Summary
Alterations of the cell surface carbohydrate structures of cancer cells are suggested to affect normal cellular interactions and have been shown to facilitate tumour cell colonisation and metastasis. The cancer-associated changes include underexpression and overexpression of naturally occurring glycans, the appearance of incomplete or truncated structures, the appearance of novel structures, and neoexpression of glycans normally restricted to embryonic tissues [1,2,3]. One such frequently observed membrane modification is altered expression of β1-6-branched N-linked glycans, caused by increased transcription and activity of β1,6-N-acetylglucosaminyltransferase V (GnT-V). Another one of these membrane-bound CAMs, known to be a valuable marker for poor prognosis in several types of cancer, is the L1cell adhesion molecule
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