HG-38INHIBITING PBX-HOX BINDING IN PAEDIATRIC GLIOMA STEM CELLS AS A NOVEL THERAPEUTIC TREATMENT IN GLIOBLASTOMA

Abstract

HG-38. INHIBITING PBX-HOX BINDING IN PAEDIATRIC GLIOMA STEM CELLS AS A NOVEL THERAPEUTIC TREATMENT IN GLIOBLASTOMA William Rogers1, Richard Morgan2, and Hardev Pandha1; University of Surrey, Guildford, Surrey, UK; University of Bradford, Bradford, West Yorkshire, UK INTRODUCTION: The HOX genes encode a familyof transcription factors that play an essential role in embryonic patterning, but are dysregulated in numerous cancers, including glioblastoma. Previous research indicates that all HOX genes are expressed at varying levels in glioblastoma cells, but are highly expressed in glioma stem cells. Previously we reported that disrupting HOX-PBX binding using the HXR9 peptide induced adult glioblastoma cell lines to undergo apoptosis, and that glioma stem cells were the most sensitive to HXR9-mediated killing. In this study we assessed whether HXR9 could also kill paediatric glioma stem cells. METHODS: HOX and PBX expression was determined using quantitative RT-PCR. Glioma cell lines were enriched for glioma stem cells and evaluated for the presence of stem cell markers. Glioma and glioma stem cells were then treated with HXR9, and cell viability was determined by MTS assay. RESULTS: Glioma cell lines showed elevated HOX and PBX expression compared to normal astrocytes, with glioma stem cells exhibiting the highest expression levels. HXR9 showed dose dependent cytotoxicity in all cell lines, and glioma stem cells were the most sensitive. CONCLUSION: Initial results show that HOX and PBX genes are aberrantly expressed in paediatric glioma cells, with glioma stem cells showing the highest expression levels. HXR9 is cytotoxic against glioma cells and glioma stem cells. FUTURE WORK: To assess the expression levels of HOX and PBX genes in normal paediatric brains, to study the mechanism of HXR9-induced cell death, and determine the downstream genes affected by HXR9 treatment. Neuro-Oncology 18:iii48–iii77, 2016. doi:10.1093/neuonc/now073.35 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.