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Neoplastic transformation has been associated with a variety of structural changes in cell surface carbohydrates, most notably increased sialylation and β1-6-linked branching of complex-type asparagine (Asn)-linked oligosaccharides (that is, -GlcNAcβ1-6Manα1-6Manβ1-). However, little is known about the relevant glycoproteins or how these transformation-related changes in oligosaccharide biosynthesis may affect the malignant phenotype. Here it is reported that a cell surface glycoprotein, gp130, is a major target of increased β1-6-linked branching and that the expression of these oligosaccharide structures is directly related to the metastatic potential of the cells. Glycosylation mutants of a metastatic tumor cell line were selected that are deficient in both β1-6 GlcNAc transferase V activity and metastatic potential in situ. Moreover, induction of increased β1-6 branching in clones of a nonmetastatic murine …