Control of metastasis by Asn-linked, 1-6 branched oligosaccharides in mouse mammary cancer cells

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Abstract
Studies in cell lines and malignant human tissues have shown that increased cell-surface Asn-linked β1–6(GlcNAcβ1–6Man) branching is associated with increased tumorigenic and metastatic properties. In this study, three mouse mammary cancer cell lines were transfected with an expression vector containing the mouse cDNA for N-acetylglucosaminyltransferase V (GlcNAcT-V EC 2.4.1.155), the glycosyltransferase responsible for initiating β1–6 branching on Asn-linked carbohydrates. The cell lines were screened for increased cytotoxicity to L-PHA, a lectin specific for β1–6 branching structures. Cell lines exhibiting increased L-PHA cytotoxicity expressed increased levels of β1–6 branching structures. Northern blots detected the presence of GlcNAcT-V transcribed from the expression vector in the L-PHA sensitive cell lines. After injection into the tail veins of mice, transfected cell lines with increased β1–6 branching on the cell surface formed elevated levels of lung tumors relative to control transfected cell lines (P < 0.002). Western blots of membrane proteins from GlcNAcT-V transfected and control cells probed with the lectins DSA and WGA did not show an increase in polyN-acetyllactosamine and sialic acid content in the transfected cell lines. These results demonstrate that a specific increase in β1–6 branching due to an elevation in GlcNAcT-V expression increases metastatic potential.