The glycobiology of brain tumors: disease relevance and therapeutic potential

Abstract

The oligosaccharides that decorate cell surface glycoconjugates play important roles in intercellular recognition and cell–extracellular matrix interactions, and thus the regulation of cellular migration, metastasis and invasivity. Virtually all tumor cells display aberrant cell-surface glycosylation patterns brought about by alterations in their biosynthetic machinery. This holds true for highly invasive, malignant brain tumors as well as tumor cells that metastasize to the brain. The field of glycobiology is well established with essentially all of the biochemical pathways for oligosaccharide metabolism characterized and all of the ‘glycogenes’ involved in these pathways cloned. Yet there has been a paucity of progress toward the development of therapeutics. However, recent studies aimed at controlled glycosylation of therapeutic antibodies and mucins with anticancer vaccine potential, the emergence of new and highly sensitive tools for the identification of tumor-associated biomarkers and the manipulation of the expression of glycogenes that inhibit brain tumor invasivity have emerged. The opportunity now exists to answer questions as to how glycogenes are regulated at the genomic and transcriptomic level and how altered glycogene expression patterns lead to altered cell surface glycoconjugates. These studies should lead to the development of ways to directly regulate tumor cell glycogene expression, which should have significant therapeutic potential.

Keywords::

• cell surface glycoconjugate
• ganglioside
• gene therapy
• glioma
• glycosyltransferase gene
• integrin
• invasivity
• microarray

Acknowledgements

The authors would like to acknowledge the technical assistance of Ms Donna Kersey and to thank Professor Bayar Thimmapaya for providing the adenoviral vector.

Financial & competing interests disclosure

This work was supported in part by grants from the Falk Foundation (Chicago, IL, USA), Brach and Buchanan Foundations (Chicago, IL, USA), The Mizutani Foundation (Japan), Globe Foundation (Phoenix, AZ, USA), The American Heart Association and The American Brain Tumor Association. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed

No writing assistance was utilized in the production of this manuscript.