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Replication Study: Wnt activity defines colon cancer stem cells and is regulated by the microenvironment

As part of the Reproducibility Project: Cancer Biology we published a Registered Report (Evans et al., 2015), that described how we intended to replicate selected experiments from the paper ‘Wnt activity defines colon cancer stem cells and is regulated by the microenvironment’ (Vermeulen et al., 201...

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Autores principales: Essex, Anthony, Pineda, Javier, Acharya, Grishma, Xin, Hong, Evans, James
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584130/
https://www.ncbi.nlm.nih.gov/pubmed/31215867
http://dx.doi.org/10.7554/eLife.45426
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author Essex, Anthony
Pineda, Javier
Acharya, Grishma
Xin, Hong
Evans, James
author_facet Essex, Anthony
Pineda, Javier
Acharya, Grishma
Xin, Hong
Evans, James
author_sort Essex, Anthony
collection PubMed
description As part of the Reproducibility Project: Cancer Biology we published a Registered Report (Evans et al., 2015), that described how we intended to replicate selected experiments from the paper ‘Wnt activity defines colon cancer stem cells and is regulated by the microenvironment’ (Vermeulen et al., 2010). Here, we report the results. Using three independent primary spheroidal colon cancer cultures that expressed a Wnt reporter construct we observed high Wnt activity was associated with the cell surface markers CD133, CD166, and CD29, but not CD24 and CD44, while the original study found all five markers were correlated with high Wnt activity (Figure 2F; Vermeulen et al., 2010). Clonogenicity was highest in cells with high Wnt activity and clonogenic potential of cells with low Wnt activity were increased by myofibroblast-secreted factors, including HGF. While the effects were in the same direction as the original study (Figure 6D; Vermeulen et al., 2010) whether statistical significance was reached among the different conditions varied. When tested in vivo, we did not find a difference in tumorigenicity between high and low Wnt activity, while the original study found cells with high Wnt activity were more effective in inducing tumors (Figure 7E; Vermeulen et al., 2010). Tumorigenicity, however, was increased with myofibroblast-secreted factors, which was in the same direction as the original study (Figure 7E; Vermeulen et al., 2010), but not statistically significant. Finally, we report meta-analyses for each results where possible.
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spelling pubmed-65841302019-06-21 Replication Study: Wnt activity defines colon cancer stem cells and is regulated by the microenvironment Essex, Anthony Pineda, Javier Acharya, Grishma Xin, Hong Evans, James eLife Cancer Biology As part of the Reproducibility Project: Cancer Biology we published a Registered Report (Evans et al., 2015), that described how we intended to replicate selected experiments from the paper ‘Wnt activity defines colon cancer stem cells and is regulated by the microenvironment’ (Vermeulen et al., 2010). Here, we report the results. Using three independent primary spheroidal colon cancer cultures that expressed a Wnt reporter construct we observed high Wnt activity was associated with the cell surface markers CD133, CD166, and CD29, but not CD24 and CD44, while the original study found all five markers were correlated with high Wnt activity (Figure 2F; Vermeulen et al., 2010). Clonogenicity was highest in cells with high Wnt activity and clonogenic potential of cells with low Wnt activity were increased by myofibroblast-secreted factors, including HGF. While the effects were in the same direction as the original study (Figure 6D; Vermeulen et al., 2010) whether statistical significance was reached among the different conditions varied. When tested in vivo, we did not find a difference in tumorigenicity between high and low Wnt activity, while the original study found cells with high Wnt activity were more effective in inducing tumors (Figure 7E; Vermeulen et al., 2010). Tumorigenicity, however, was increased with myofibroblast-secreted factors, which was in the same direction as the original study (Figure 7E; Vermeulen et al., 2010), but not statistically significant. Finally, we report meta-analyses for each results where possible. eLife Sciences Publications, Ltd 2019-06-19 /pmc/articles/PMC6584130/ /pubmed/31215867 http://dx.doi.org/10.7554/eLife.45426 Text en © 2019, Essex et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cancer Biology
Essex, Anthony
Pineda, Javier
Acharya, Grishma
Xin, Hong
Evans, James
Replication Study: Wnt activity defines colon cancer stem cells and is regulated by the microenvironment
title Replication Study: Wnt activity defines colon cancer stem cells and is regulated by the microenvironment
title_full Replication Study: Wnt activity defines colon cancer stem cells and is regulated by the microenvironment
title_fullStr Replication Study: Wnt activity defines colon cancer stem cells and is regulated by the microenvironment
title_full_unstemmed Replication Study: Wnt activity defines colon cancer stem cells and is regulated by the microenvironment
title_short Replication Study: Wnt activity defines colon cancer stem cells and is regulated by the microenvironment
title_sort replication study: wnt activity defines colon cancer stem cells and is regulated by the microenvironment
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584130/
https://www.ncbi.nlm.nih.gov/pubmed/31215867
http://dx.doi.org/10.7554/eLife.45426
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