Phenotypic Plasticity in Uveal Melanoma Is Not Restricted to a Tumor Subpopulation and Is Unrelated to Cancer Stem Cell Characteristics

DOHERTY, Rachel E., SISLEY, Karen, HAMMOND, David W., RENNIE, Ian G. and CROSS, Neil (2017). Phenotypic Plasticity in Uveal Melanoma Is Not Restricted to a Tumor Subpopulation and Is Unrelated to Cancer Stem Cell Characteristics. Investigative Opthalmology & Visual Science, 58 (12), p. 5387.

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Link to published version:: 10.1167/iovs.17-22272

Abstract

Purpose: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and approximately half of those diagnosed will die of metastasis. This study investigates whether UM progression is driven by a subpopulation of stem-like cells, termed “cancer stem cells” (CSCs). Methods: Expression of postulated stem cell markers aldehyde dehydrogenase (ALDH), CD44, and CD133 was analyzed in UM cell lines and primary UM short-term cultures (STCs) established from tumor samples. Additionally, the notion of a “cellular hierarchy” within UM was investigated. Finally, the phenomenon of phenotypic plasticity in response to environmental factors was explored. Results: We demonstrate that expression of ALDH, CD44, and CD133 does not select for a subpopulation of stem-like cells in either UM cell lines or UM STCs. Furthermore, there is an absence of a cellular hierarchy in cell lines and all cells in culture are able to drive tumor progression. Last, we show that established UM cell lines and UM STCs are plastic in nature and switch their phenotype in response to environmental stimuli. Conclusions: We hypothesize that this capacity to undergo phenotypic plasticity may be a consequence of neural crest lineage and renders the exploration of the CSC hypothesis extremely challenging in UM.

Item Type: Article
Additional Information: ** Embargo End Date: 19-10-2017 ** From Crossref via Jisc Publications Router. ** Licence for vor version of this article starting on 19-10-2017: http://creativecommons.org/licenses/by-nc-nd/4.0/
Research Institute, Centre or Group: Biomolecular Sciences Research Centre
Identification Number: 10.1167/iovs.17-22272
Related URLs:
SWORD Depositor: Hilary Ridgway
Depositing User: Hilary Ridgway
Date Deposited: 27 Oct 2017 09:08
Last Modified: 28 Oct 2017 08:50
URI: http://shura.shu.ac.uk/id/eprint/17151

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