P57 * STEM CELL PLASTICITY AND TUMORIGENISIS: REGULATORY ROLES OF HEPARAN SULPHATE IN THE CANCER STEM CELL NICHE

Abstract

INTRODUCTION: During the past few years, stem cells have received attention as a system for research and cell-based therapies due to their unique ability for self-renewal. However, concerns have arisen from our current knowledge regarding what permits a safe use of stem cells in tissue engineering strategies. Uncontrolled stem cell expansion is a major cause of cancer and tissue degeneration. Sub- populations of cancer cells have been identified in tumours, leading to the cancer stem cell hypothesis, and the potential to target these cells for effective new anti-cancer therapies. METHOD: Systems to be studied will include the role of extracellular HS on neuroblastoma cell lines influence on the phenotype of cancer cell lines. The methods to be used will include: neuroblastoma cell culture; proliferation and differentiaton assays, Immunophenotyping by fluorescent activated cell sorting (FACS) analysis, chemical biology (HS saccharide libraries & synthetic compounds), glycoanalysis (glycan purification; HPLC/FPLC, and glycan analysis) to study changes in HS molecular phenotype with neuroblastoma cells. RESULTS: When we analysed heparin- treated SKNAS cells by flow cytometry to identify the CD44+ sub-population, we observed that low concentrations of heparin (10 ng/ml) reduced the proportion of CD44+ cells in culture. Conversely, treatment with a modified (desulphated) heparin, the F3 compound, known to have anti-metastatic activity have shown no significant effect. on the proportion of CD44+ cells in the SKNAS cell cultures. CONCLUSION:These results suggest that: a) heparinoid compounds may be effective in reducing the proportion of CSCs in a tumour; b) this effect may have some selectivity for to certain HS structures, since highly sulphated heparin displayed differentially activity compared to a low sulphated heparin derivative.