β1-6 Branching of Asn-Linked Oligosaccharides Is Directly Associated with Metastasis

Abstract

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 mammary carcinoma correlated strongly with acquisition of metastatic potential. The results indicate that increased β1-6-linked branching of complex-type oligosaccharides on gp130 may be an important feature of tumor progression related to increased metastatic potential.