+441518081136microRNA-17 IS DOWNREGULATED IN ESOPHAGEAL ADENOCARCINOMA CANCER STEM-LIKE CELLS AND PROMOTES A RADIORESISTANT PHENOTYPE
11th International Conference on Cancer Stem Cells and Oncology Research
June 11-13, 2018 | Dublin, Ireland
Stephen G Maher,Niamh Lynam-Lennon, Susan Heavey, Gary Sommerville, Becky A.S. Bibby, Brendan Ffrench, Jennifer Quinn, Michael F Gallagher and John V Reynolds
Trinity Translational Medicine Institute, Ireland University of Hull, United Kingdom
Posters & Accepted Abstracts : J Med Oncl Ther
Abstract:
Esophageal adenocarcinoma (EAC) is an aggressive disease with an extremely poor prognosis. Resistance to neoadjuvant chemoradiation therapy (CRT) remains a critical barrier to the effective treatment of EAC. Cancer stem-like cells (CSC) are a distinct subpopulation of cells implicated in the resistance of tumors to anti-cancer therapy. However, their role in the resistance of EAC to CRT is largely unknown. In this study, using a novel in vitro isogenic model of radioresistant EAC, we demonstrate that radioresistant EAC cells have enhanced tumorigenicity in vivo, increased expression of CSCassociated markers and enhanced holoclone forming ability. Further investigation identified a subpopulation of CSC that are characterised by high aldehyde dehydrogenase (ALDH) activity, enhanced radioresistance and significantly altered microRNA (miR) expression alterations, including decreased expression of miR-17. In vitro, miR-17 overexpression was demonstrated to significantly sensitise radioresistant cells to X-ray radiation and promoted the downregulation of genes with miR-17 binding sites, such as C6orf120. In vivo, miR-17 was significantly decreased, whilst C6orf120 was significantly increased, in pre-treatment EAC tumour samples from patients who demonstrated a poor response to neoadjuvant CRT. This study sheds novel insights into the role of CSC in the resistance of EAC to CRT and highlights miR-17 as a potential biomarker of CRT sensitivity and novel therapeutic target in treatment resistant EAC. Maherst@tcd.ie
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