CD10/ALDH cells are the sole cisplatin-resistant component of a novel ovarian cancer stem cell hierarchy.
Mahgoub, Thamir Mahmoud
Hennessy, Bryan T
O'Leary, John J
Gallagher, Michael F
Affiliation1 Department of Histopathology, Trinity College Dublin, Central Pathology Laboratory, St. James's Hospital, Dublin 8, Ireland. 2 Pathology Research Laboratory, Coombe Women and Infant's University Hospital, Dublin 8, Ireland. 3 Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland. 4 Department of Obstetrics and Gynaecology, Trinity College Dublin, Trinity Centre for Health Sciences, St. James's Hospital, Dublin 8, Ireland. 5 School of Biological Sciences, Dublin Institute of Technology, Kevin Street, Dublin, Ireland. 6 Department of Clinical Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland. 7 Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin 2, Ireland. 8 Department of Natural Sciences, Middlesex University, Hendon, London, UK.
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CitationCell Death and Disease (2017) 8, e3128; doi:10.1038/cddis.2017.379
JournalCell Death & Disease
AbstractIt is long established that tumour-initiating cancer stem cells (CSCs) possess chemoresistant properties. However, little is known of the mechanisms involved, particularly with respect to the organisation of CSCs as stem-progenitor-differentiated cell hierarchies. Here we aimed to elucidate the relationship between CSC hierarchies and chemoresistance in an ovarian cancer model. Using a single cell-based approach to CSC discovery and validation, we report a novel, four-component CSC hierarchy based around the markers cluster of differentiation 10 (CD10) and aldehyde dehydrogenase (ALDH). In a change to our understanding of CSC biology, resistance to chemotherapy drug cisplatin was found to be the sole property of CD10
SponsorsThis study was primarily supported by The Emer Casey Foundation (to BF, JOL). Researchers were supported by further funding from The Irish Cancer Society (to MG, JOL), Science Foundation Ireland (to JOL) and Health Research Board (Ireland) (to JOL). We thank Professor Peter Andrews, University of Sheffield for his technical advice and support throughout the study. We also thank Dr. Eamon Breen (IMM, TCD) and Dr. Barry Moran (TBSI, TCD) for their help with flow cytometry. Funding for the flow cytometry facility (TBSI, TCD) was provided by Science Foundation Ireland (Grant 12/RI/2340(7)).
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