Prostate cancer-derived holoclones: a novel and effective model for evaluating cancer stemness

Abstract Prostate cancer accounts for approximately 13.5% of all newly diagnosed male cancer cases. Significant clinical burdens remain in terms of ineffective prognostication, with overtreatment of insignificant disease. Additionally, the pathobiology underlying disease heterogeneity remains poorly...

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Autores principales:	Louise Flynn, Martin P. Barr, Anne-Marie Baird, Paul Smyth, Orla M. Casey, Gordon Blackshields, John Greene, Stephen R. Pennington, Emily Hams, Padraic G. Fallon, John O’Leary, Orla Sheils, Stephen P. Finn
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d612e913180e4043beedde23937a643d
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spelling	oai:doaj.org-article:d612e913180e4043beedde23937a643d2021-12-02T15:39:49ZProstate cancer-derived holoclones: a novel and effective model for evaluating cancer stemness10.1038/s41598-020-68187-92045-2322https://doaj.org/article/d612e913180e4043beedde23937a643d2020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-68187-9https://doaj.org/toc/2045-2322Abstract Prostate cancer accounts for approximately 13.5% of all newly diagnosed male cancer cases. Significant clinical burdens remain in terms of ineffective prognostication, with overtreatment of insignificant disease. Additionally, the pathobiology underlying disease heterogeneity remains poorly understood. As the role of cancer stem cells in the perpetuation of aggressive carcinoma is being substantiated by experimental evidence, it is crucially important to understand the molecular mechanisms, which regulate key features of cancer stem cells. We investigated two methods for in vitro cultivation of putative prostate cancer stem cells based on ‘high-salt agar’ and ‘monoclonal cultivation’. Data demonstrated ‘monoclonal cultivation’ as the superior method. We demonstrated that ‘holoclones’ expressed canonical stem markers, retained the exclusive ability to generate poorly differentiated tumours in NOD/SCID mice and possessed a unique mRNA-miRNA gene signature. miRNA:Target interactions analysis visualised potentially critical regulatory networks, which are dysregulated in prostate cancer holoclones. The characterisation of this tumorigenic population lays the groundwork for this model to be used in the identification of proteomic or small non-coding RNA therapeutic targets for the eradication of this critical cellular population. This is significant, as it provides a potential route to limit development of aggressive disease and thus improve survival rates.Louise FlynnMartin P. BarrAnne-Marie BairdPaul SmythOrla M. CaseyGordon BlackshieldsJohn GreeneStephen R. PenningtonEmily HamsPadraic G. FallonJohn O’LearyOrla SheilsStephen P. FinnNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-17 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Louise Flynn Martin P. Barr Anne-Marie Baird Paul Smyth Orla M. Casey Gordon Blackshields John Greene Stephen R. Pennington Emily Hams Padraic G. Fallon John O’Leary Orla Sheils Stephen P. Finn Prostate cancer-derived holoclones: a novel and effective model for evaluating cancer stemness
description	Abstract Prostate cancer accounts for approximately 13.5% of all newly diagnosed male cancer cases. Significant clinical burdens remain in terms of ineffective prognostication, with overtreatment of insignificant disease. Additionally, the pathobiology underlying disease heterogeneity remains poorly understood. As the role of cancer stem cells in the perpetuation of aggressive carcinoma is being substantiated by experimental evidence, it is crucially important to understand the molecular mechanisms, which regulate key features of cancer stem cells. We investigated two methods for in vitro cultivation of putative prostate cancer stem cells based on ‘high-salt agar’ and ‘monoclonal cultivation’. Data demonstrated ‘monoclonal cultivation’ as the superior method. We demonstrated that ‘holoclones’ expressed canonical stem markers, retained the exclusive ability to generate poorly differentiated tumours in NOD/SCID mice and possessed a unique mRNA-miRNA gene signature. miRNA:Target interactions analysis visualised potentially critical regulatory networks, which are dysregulated in prostate cancer holoclones. The characterisation of this tumorigenic population lays the groundwork for this model to be used in the identification of proteomic or small non-coding RNA therapeutic targets for the eradication of this critical cellular population. This is significant, as it provides a potential route to limit development of aggressive disease and thus improve survival rates.
format	article
author	Louise Flynn Martin P. Barr Anne-Marie Baird Paul Smyth Orla M. Casey Gordon Blackshields John Greene Stephen R. Pennington Emily Hams Padraic G. Fallon John O’Leary Orla Sheils Stephen P. Finn
author_facet	Louise Flynn Martin P. Barr Anne-Marie Baird Paul Smyth Orla M. Casey Gordon Blackshields John Greene Stephen R. Pennington Emily Hams Padraic G. Fallon John O’Leary Orla Sheils Stephen P. Finn
author_sort	Louise Flynn
title	Prostate cancer-derived holoclones: a novel and effective model for evaluating cancer stemness
title_short	Prostate cancer-derived holoclones: a novel and effective model for evaluating cancer stemness
title_full	Prostate cancer-derived holoclones: a novel and effective model for evaluating cancer stemness
title_fullStr	Prostate cancer-derived holoclones: a novel and effective model for evaluating cancer stemness
title_full_unstemmed	Prostate cancer-derived holoclones: a novel and effective model for evaluating cancer stemness
title_sort	prostate cancer-derived holoclones: a novel and effective model for evaluating cancer stemness
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/d612e913180e4043beedde23937a643d
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Prostate cancer-derived holoclones: a novel and effective model for evaluating cancer stemness

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