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

TLDR

Neoplastic transformation is linked to changes in cell surface carbohydrates, especially increased β1‑6‑linked branching of complex-type Asn‑linked oligosaccharides, yet the specific glycoproteins involved and their impact on malignancy remain poorly understood. The study shows that increased β1‑6‑linked branching on the cell surface glycoprotein gp130 correlates with, and appears to drive, metastatic potential, as loss of β1‑6 GlcNAc transferase V activity reduces metastasis and artificial induction of this branching in nonmetastatic cells promotes 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.