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Investigating the molecular and structural basis for the anti cancer cell adhesion properties of pectin galactans

Reference	BBS/E/F/00042548
Principal Investigator / Supervisor	Professor Nathalie Juge
Co-Investigators / Co-Supervisors	Professor Victor Morris
Institution	Quadram Institute Bioscience
Department	Quadram Institute Bioscience Department
Funding type	Research
Value (£)	66,900
Status	Completed
Type	Institute Project
Start date	01/10/2009
End date	30/09/2010
Duration	12 months

Abstract

Altered mucin 1 (MUC1) secretion/glycosylation patterns have been implicated in several cancerous conditions including gastric, colorectal and breast carcinomas. In particular, an association between the expression of MUC1, Thomsen-Friedenreich (TF) glycoantigen (Gal beta1–3GalNAc), and beta-galactoside-binding lectin galectin-3 (gal3) was recently reported to promote cancer cell adhesion to the endothelium. The involvement of galectins as pleiotropic regulators of cell adhesion and growth in disease progression explains the interest to define their ligand-binding properties. It has been proposed that pectic polysaccharides can act by binding to and inhibiting the various roles of the mammalian gal3 in cancer progression and metastasis and we have recently characterised galactan fragments binding to gal3. In the present study, we aim to investigate whether these pectin fragments can specifically disrupt the MUC1 TF antigen/gal3 interactions in vitro and in cell cultures. The project benefits from the complementary expertise in food carbohydrate biochemistry at the Institute of Food Research (IFR) and tumour cell-endothelial cell biology at the University of East Anglia (UEA). Combining experimental information from the binding data (in vitro and in cells) and X-ray crystal structures of galectin–carbohydrate ligand complexes derived from this "Pump priming grant" will enable the design of dietary carbohydrate compounds as agents for the prevention and/or treatment of cancer in the future. Natural carbohydrates have the advantage of being non-toxic therapies plus the long-term potential of protection in the diet.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Structural Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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