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

Abstract 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. Accountin...

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Autores principales:	Jorge Fernandez-de-Cossio-Diaz, Andrea De Martino, Roberto Mulet
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/acdfbc10cd054f6e83d572d0d68f32e0
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spelling	oai:doaj.org-article:acdfbc10cd054f6e83d572d0d68f32e02021-12-02T12:32:02ZMicroenvironmental cooperation promotes early spread and bistability of a Warburg-like phenotype10.1038/s41598-017-03342-32045-2322https://doaj.org/article/acdfbc10cd054f6e83d572d0d68f32e02017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03342-3https://doaj.org/toc/2045-2322Abstract 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.Jorge Fernandez-de-Cossio-DiazAndrea De MartinoRoberto MuletNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jorge Fernandez-de-Cossio-Diaz Andrea De Martino Roberto Mulet Microenvironmental cooperation promotes early spread and bistability of a Warburg-like phenotype
description	Abstract 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.
format	article
author	Jorge Fernandez-de-Cossio-Diaz Andrea De Martino Roberto Mulet
author_facet	Jorge Fernandez-de-Cossio-Diaz Andrea De Martino Roberto Mulet
author_sort	Jorge Fernandez-de-Cossio-Diaz
title	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_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_sort	microenvironmental cooperation promotes early spread and bistability of a warburg-like phenotype
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/acdfbc10cd054f6e83d572d0d68f32e0
work_keys_str_mv	AT jorgefernandezdecossiodiaz microenvironmentalcooperationpromotesearlyspreadandbistabilityofawarburglikephenotype AT andreademartino microenvironmentalcooperationpromotesearlyspreadandbistabilityofawarburglikephenotype AT robertomulet microenvironmentalcooperationpromotesearlyspreadandbistabilityofawarburglikephenotype
_version_	1718394234907656192

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

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