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How is the evolution of tumour resistance at organ-scale impacted by the importance of the organ for fitness?

BACKGROUND: A strong variability in cancer incidence is observed between human organs. Recently, it has been suggested that the relative contribution of organs to organism fitness (reproduction or survival) could explain at least a part of the observed variation. The objective of this study is to in...

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Autores principales: Gidoin, Cindy, Ujvari, Beata, Thomas, Frédéric, Roche, Benjamin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282255/
https://www.ncbi.nlm.nih.gov/pubmed/30522441
http://dx.doi.org/10.1186/s12862-018-1298-7
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author Gidoin, Cindy
Ujvari, Beata
Thomas, Frédéric
Roche, Benjamin
author_facet Gidoin, Cindy
Ujvari, Beata
Thomas, Frédéric
Roche, Benjamin
author_sort Gidoin, Cindy
collection PubMed
description BACKGROUND: A strong variability in cancer incidence is observed between human organs. Recently, it has been suggested that the relative contribution of organs to organism fitness (reproduction or survival) could explain at least a part of the observed variation. The objective of this study is to investigate theoretically the main factors driving the evolution of tumour resistance mechanisms of organs when their relative contribution to organism fitness is considered. We use a population-scale model where individuals can develop a tumour in a key organ (i.e. in which even a small tumour can negatively impact organism fitness), an auxiliary organ (i.e. in which only a large tumour has a relatively significant impact) or both organs because of metastasis. RESULTS: Our simulations show that natural selection acts in two different ways to prevent cancer in a key and an auxiliary organs. In the key organ, the strategy mostly selected is the highest resistance and only a high cost of resistance mitigates this behavior. Inversely, we observe that a low resistance strategy can be selected in the auxiliary organ when the development of the tumour is slow and the effect of a large tumour on the mortality of the organism is relatively weak. Nevertheless, if the tumour can spread to a key organ, higher resistance strategies are selected in the auxiliary organ. CONCLUSION: Finally, our study demonstrates that the relative contribution of organs to the organism fitness and the metastatic propensity of the tumour influence the evolution of tumour resistance at organ scale and should be considered by studies aiming to explain the variability in cancer incidence at organ-scale. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12862-018-1298-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-62822552018-12-10 How is the evolution of tumour resistance at organ-scale impacted by the importance of the organ for fitness? Gidoin, Cindy Ujvari, Beata Thomas, Frédéric Roche, Benjamin BMC Evol Biol Research Article BACKGROUND: A strong variability in cancer incidence is observed between human organs. Recently, it has been suggested that the relative contribution of organs to organism fitness (reproduction or survival) could explain at least a part of the observed variation. The objective of this study is to investigate theoretically the main factors driving the evolution of tumour resistance mechanisms of organs when their relative contribution to organism fitness is considered. We use a population-scale model where individuals can develop a tumour in a key organ (i.e. in which even a small tumour can negatively impact organism fitness), an auxiliary organ (i.e. in which only a large tumour has a relatively significant impact) or both organs because of metastasis. RESULTS: Our simulations show that natural selection acts in two different ways to prevent cancer in a key and an auxiliary organs. In the key organ, the strategy mostly selected is the highest resistance and only a high cost of resistance mitigates this behavior. Inversely, we observe that a low resistance strategy can be selected in the auxiliary organ when the development of the tumour is slow and the effect of a large tumour on the mortality of the organism is relatively weak. Nevertheless, if the tumour can spread to a key organ, higher resistance strategies are selected in the auxiliary organ. CONCLUSION: Finally, our study demonstrates that the relative contribution of organs to the organism fitness and the metastatic propensity of the tumour influence the evolution of tumour resistance at organ scale and should be considered by studies aiming to explain the variability in cancer incidence at organ-scale. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12862-018-1298-7) contains supplementary material, which is available to authorized users. BioMed Central 2018-12-06 /pmc/articles/PMC6282255/ /pubmed/30522441 http://dx.doi.org/10.1186/s12862-018-1298-7 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Gidoin, Cindy
Ujvari, Beata
Thomas, Frédéric
Roche, Benjamin
How is the evolution of tumour resistance at organ-scale impacted by the importance of the organ for fitness?
title How is the evolution of tumour resistance at organ-scale impacted by the importance of the organ for fitness?
title_full How is the evolution of tumour resistance at organ-scale impacted by the importance of the organ for fitness?
title_fullStr How is the evolution of tumour resistance at organ-scale impacted by the importance of the organ for fitness?
title_full_unstemmed How is the evolution of tumour resistance at organ-scale impacted by the importance of the organ for fitness?
title_short How is the evolution of tumour resistance at organ-scale impacted by the importance of the organ for fitness?
title_sort how is the evolution of tumour resistance at organ-scale impacted by the importance of the organ for fitness?
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282255/
https://www.ncbi.nlm.nih.gov/pubmed/30522441
http://dx.doi.org/10.1186/s12862-018-1298-7
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