- Title
- Cancer stem cells are underestimated by standard experimental methods in clear cell renal cell carcinoma
- Creator
- Gedye, Craig; Sirskyj, Danylo; Evans, Andrew; Finelli, Antonio; Jewett, Michael A. S.; Ailles, Laurie E.; Lobo, Nazleen C.; Meens, Jalna; Hyatt, Elzbieta; Robinette, Michael; Fleshner, Neil; Hamilton, Robert J.; Kulkarni, Girish; Zlotta, Alexandre
- Relation
- Scientific Reports Vol. 6
- Publisher Link
- http://dx.doi.org/10.1038/srep25220
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2016
- Description
- Rare cancer stem cells (CSC) are proposed to be responsible for tumour propagation and re-initiation and are functionally defined by identifying tumour-initiating cells (TICs) using the xenotransplantation limiting dilution assay (LDA). While TICs in clear cell renal cell carcinoma (ccRCC) appeared rare in NOD/SCID/IL2Rγ 3 -/- (NSG) mice, xenografts formed more efficiently from small tumour fragments, indicating the LDA underestimated ccRCC TIC frequency. Mechanistic interrogation of the LDA identified multiple steps that influence ccRCC TIC quantitation. For example, tissue disaggregation destroys most ccRCC cells, common assays significantly overestimate tumour cell viability, and microenvironmental supplementation with human extracellular factors or pharmacological inhibition of anoikis increase clonogenicity and tumourigenicity of ccRCC cell lines and primary tumour cells. Identification of these previously uncharacterized concerns that cumulatively lead to substantial underestimation of TICs in ccRCC provides a framework for development of more accurate TIC assays in the future, both for this disease and for other cancers.
- Subject
- cancer stem cells (CSC); clear cells; renal cell carcinoma
- Identifier
- http://hdl.handle.net/1959.13/1323559
- Identifier
- uon:24837
- Identifier
- ISSN:2045-2322
- Rights
- This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
- Language
- eng
- Full Text
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