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Microenvironmental cooperation promotes early spread and bistability of a Warburg-like phenotype

We introduce an in silico model for the initial spread of an aberrant phenotype with Warburg-like overflow metabolism within a healthy homeostatic tissue in contact with a nutrient reservoir (the blood), aimed at characterizing the role of the microenvironment for aberrant growth. Accounting for cel...

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Detalles Bibliográficos
Autores principales: Fernandez-de-Cossio-Diaz, Jorge, De Martino, Andrea, Mulet, Roberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465218/
https://www.ncbi.nlm.nih.gov/pubmed/28596605
http://dx.doi.org/10.1038/s41598-017-03342-3
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author Fernandez-de-Cossio-Diaz, Jorge
De Martino, Andrea
Mulet, Roberto
author_facet Fernandez-de-Cossio-Diaz, Jorge
De Martino, Andrea
Mulet, Roberto
author_sort Fernandez-de-Cossio-Diaz, Jorge
collection PubMed
description We introduce an in silico model for the initial spread of an aberrant phenotype with Warburg-like overflow metabolism within a healthy homeostatic tissue in contact with a nutrient reservoir (the blood), aimed at characterizing the role of the microenvironment for aberrant growth. Accounting for cellular metabolic activity, competition for nutrients, spatial diffusion and their feedbacks on aberrant replication and death rates, we obtain a phase portrait where distinct asymptotic whole-tissue states are found upon varying the tissue-blood turnover rate and the level of blood-borne primary nutrient. Over a broad range of parameters, the spreading dynamics is bistable as random fluctuations can impact the final state of the tissue. Such a behaviour turns out to be linked to the re-cycling of overflow products by non-aberrant cells. Quantitative insight on the overall emerging picture is provided by a spatially homogeneous version of the model.
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spelling pubmed-54652182017-06-14 Microenvironmental cooperation promotes early spread and bistability of a Warburg-like phenotype Fernandez-de-Cossio-Diaz, Jorge De Martino, Andrea Mulet, Roberto Sci Rep Article We introduce an in silico model for the initial spread of an aberrant phenotype with Warburg-like overflow metabolism within a healthy homeostatic tissue in contact with a nutrient reservoir (the blood), aimed at characterizing the role of the microenvironment for aberrant growth. Accounting for cellular metabolic activity, competition for nutrients, spatial diffusion and their feedbacks on aberrant replication and death rates, we obtain a phase portrait where distinct asymptotic whole-tissue states are found upon varying the tissue-blood turnover rate and the level of blood-borne primary nutrient. Over a broad range of parameters, the spreading dynamics is bistable as random fluctuations can impact the final state of the tissue. Such a behaviour turns out to be linked to the re-cycling of overflow products by non-aberrant cells. Quantitative insight on the overall emerging picture is provided by a spatially homogeneous version of the model. Nature Publishing Group UK 2017-06-08 /pmc/articles/PMC5465218/ /pubmed/28596605 http://dx.doi.org/10.1038/s41598-017-03342-3 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Fernandez-de-Cossio-Diaz, Jorge
De Martino, Andrea
Mulet, Roberto
Microenvironmental cooperation promotes early spread and bistability of a Warburg-like phenotype
title Microenvironmental cooperation promotes early spread and bistability of a Warburg-like phenotype
title_full Microenvironmental cooperation promotes early spread and bistability of a Warburg-like phenotype
title_fullStr Microenvironmental cooperation promotes early spread and bistability of a Warburg-like phenotype
title_full_unstemmed Microenvironmental cooperation promotes early spread and bistability of a Warburg-like phenotype
title_short Microenvironmental cooperation promotes early spread and bistability of a Warburg-like phenotype
title_sort microenvironmental cooperation promotes early spread and bistability of a warburg-like phenotype
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465218/
https://www.ncbi.nlm.nih.gov/pubmed/28596605
http://dx.doi.org/10.1038/s41598-017-03342-3
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