The siatyltransferase ST3GAL6 Iniueeces homing and survival in multlple myeloma

摘要

Glycosylation is a stepwise procedure of covalent attachment of oligosaccharide chains to proteins or lipids, and alterations in this process, especially increased sialylation, have been associated with malignant transformation and metastasis. The role of altered sialylation in multiple myeloma (MM) ceil trafficking has not been previously investigated. In the present study we identified high expression of beta-galactoside alpha-2,3-sialy!transferase, ST3GAL6, in MM cell lines and patients. This gene plays a key role in selectin ligand synthesis in humans through the generation of functional sialyl Lewis X. In MRC IX patients, high expression of this gene is associated with inferior overall survival. En this study we demonstrate that knockdown of ST3GAL6 results in a significant reduction in levels of alpha-2,3-Iinked sialic acid on the surface of MM cells with an associated significant reduction in adhesion to MM bone marrow stromal cells and fibronectin along with reduced transendothelial migration in vitro.