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The sialyltransferase ST3GAL6 influences homing and survival in multiple myeloma.

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Publication Date
2014-09
ICR Author
Morgan, Gareth John
Author
Glavey, SV
Manier, S
Natoni, A
Sacco, A
Moschetta, M
Reagan, MR
Murillo, LS
Sahin, I
Wu, P
Mishima, Y
Zhang, Y
Zhang, W
Zhang, Y
Morgan, G
Joshi, L
Roccaro, AM
Ghobrial, IM
O'Dwyer, ME
Type
Journal Article
Metadata
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Abstract
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) cell trafficking has not been previously investigated. In the present study we identified high expression of β-galactoside α-2,3-sialyltransferase, 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. In this study we demonstrate that knockdown of ST3GAL6 results in a significant reduction in levels of α-2,3-linked 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. In support of our in vitro findings, we demonstrate significantly reduced homing and engraftment of ST3GAL6 knockdown MM cells to the bone marrow niche in vivo, along with decreased tumor burden and prolonged survival. This study points to the importance of altered glycosylation, particularly sialylation, in MM cell adhesion and migration.
URL
https://repository.icr.ac.uk/handle/internal/2064
Open access location
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162107/
Collections
  • Clinical Studies
  • Molecular Pathology
Version of record
10.1182/blood-2014-03-560862
Subject
Bone Marrow Cells
Cell Line, Tumor
Stromal Cells
Animals
Humans
Mice
Mice, SCID
Multiple Myeloma
N-Acetylneuraminic Acid
Sialyltransferases
Neoplasm Proteins
Cell Adhesion
Cell Survival
Female
Male
Gene Knockdown Techniques
Transendothelial and Transepithelial Migration
Human Umbilical Vein Endothelial Cells
Research team
Molecular Haematology (including Cytogenetics Group and Cell Markers)
Language
eng
License start date
2014-09
Citation
Blood, 2014, 124 (11), pp. 1765 - 1776

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