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


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
09 07 2020
Historique:
received: 10 02 2020
accepted: 19 06 2020
entrez: 11 7 2020
pubmed: 11 7 2020
medline: 1 1 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 32647229
doi: 10.1038/s41598-020-68187-9
pii: 10.1038/s41598-020-68187-9
pmc: PMC7347552
doi:

Substances chimiques

Biomarkers, Tumor 0
MicroRNAs 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

11329

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Auteurs

Louise Flynn (L)

Department of Histopathology and Morbid Anatomy, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.

Martin P Barr (MP)

Thoracic Oncology Research Group, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Dublin, Ireland.

Anne-Marie Baird (AM)

Department of Histopathology and Morbid Anatomy, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.
Thoracic Oncology Research Group, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Dublin, Ireland.

Paul Smyth (P)

Department of Histopathology and Morbid Anatomy, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.

Orla M Casey (OM)

Department of Histopathology and Morbid Anatomy, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.

Gordon Blackshields (G)

Department of Histopathology and Morbid Anatomy, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.

John Greene (J)

Department of Histopathology and Morbid Anatomy, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.

Stephen R Pennington (SR)

School of Medicine, University College Dublin, Conway Institute Belfield, Dublin, Ireland.

Emily Hams (E)

School of Medicine, Trinity Translational Medicine Institute, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.

Padraic G Fallon (PG)

School of Medicine, Trinity Translational Medicine Institute, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.

John O'Leary (J)

Department of Histopathology and Morbid Anatomy, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.
Molecular Pathology Laboratory, Coombe Women and Infant's University Hospital, Dublin, Ireland.

Orla Sheils (O)

Department of Histopathology and Morbid Anatomy, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.

Stephen P Finn (SP)

Department of Histopathology and Morbid Anatomy, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland. Stephen.Finn@tcd.ie.
Department of Histopathology, St. James's Hospital, Dublin, Ireland. Stephen.Finn@tcd.ie.

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