A bioelectric model of carcinogenesis, including propagation of cell membrane depolarization and reversal therapies

Abstract As the main theory of carcinogenesis, the Somatic Mutation Theory, increasingly presents difficulties to explain some experimental observations, different theories are being proposed. A major alternative approach is the Tissue Organization Field Theory, which explains cancer origin as a tis...

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Autor principal:	Joao Carvalho
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/93a4276832c143d7b6b8f4401694cc40
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spelling	oai:doaj.org-article:93a4276832c143d7b6b8f4401694cc402021-12-02T16:10:35ZA bioelectric model of carcinogenesis, including propagation of cell membrane depolarization and reversal therapies10.1038/s41598-021-92951-02045-2322https://doaj.org/article/93a4276832c143d7b6b8f4401694cc402021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92951-0https://doaj.org/toc/2045-2322Abstract As the main theory of carcinogenesis, the Somatic Mutation Theory, increasingly presents difficulties to explain some experimental observations, different theories are being proposed. A major alternative approach is the Tissue Organization Field Theory, which explains cancer origin as a tissue regulation disease instead of having a mainly cellular origin. This work fits in the latter hypothesis, proposing the bioelectric field, in particular the cell membrane polarization state, and ionic exchange through ion channels and gap junctions, as an important mechanism of cell communication and tissue organization and regulation. Taking into account recent experimental results and proposed bioelectric models, a computational model of cancer initiation was developed, including the propagation of a cell depolarization wave in the tissue under consideration. Cell depolarization leads to a change in its state, with the activation and deactivation of several regulation pathways, increasing cell proliferation and motility, changing its epigenetic state to a more stem cell-like behavior without the requirement of genomic mutation. The intercellular communication via gap junctions leads, in certain circumstances, to a bioelectric state propagation to neighbor cells, in a chain-like reaction, till an electric discontinuity is reached. However, this is a reversible process, and it was shown experimentally that, by implementing a therapy targeted on cell ion exchange channels, it is possible to reverse the state and repolarize cells. This mechanism can be an important alternative way in cancer prevention, diagnosis and therapy, and new experiments are proposed to test the presented hypothesis.Joao CarvalhoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joao Carvalho A bioelectric model of carcinogenesis, including propagation of cell membrane depolarization and reversal therapies
description	Abstract As the main theory of carcinogenesis, the Somatic Mutation Theory, increasingly presents difficulties to explain some experimental observations, different theories are being proposed. A major alternative approach is the Tissue Organization Field Theory, which explains cancer origin as a tissue regulation disease instead of having a mainly cellular origin. This work fits in the latter hypothesis, proposing the bioelectric field, in particular the cell membrane polarization state, and ionic exchange through ion channels and gap junctions, as an important mechanism of cell communication and tissue organization and regulation. Taking into account recent experimental results and proposed bioelectric models, a computational model of cancer initiation was developed, including the propagation of a cell depolarization wave in the tissue under consideration. Cell depolarization leads to a change in its state, with the activation and deactivation of several regulation pathways, increasing cell proliferation and motility, changing its epigenetic state to a more stem cell-like behavior without the requirement of genomic mutation. The intercellular communication via gap junctions leads, in certain circumstances, to a bioelectric state propagation to neighbor cells, in a chain-like reaction, till an electric discontinuity is reached. However, this is a reversible process, and it was shown experimentally that, by implementing a therapy targeted on cell ion exchange channels, it is possible to reverse the state and repolarize cells. This mechanism can be an important alternative way in cancer prevention, diagnosis and therapy, and new experiments are proposed to test the presented hypothesis.
format	article
author	Joao Carvalho
author_facet	Joao Carvalho
author_sort	Joao Carvalho
title	A bioelectric model of carcinogenesis, including propagation of cell membrane depolarization and reversal therapies
title_short	A bioelectric model of carcinogenesis, including propagation of cell membrane depolarization and reversal therapies
title_full	A bioelectric model of carcinogenesis, including propagation of cell membrane depolarization and reversal therapies
title_fullStr	A bioelectric model of carcinogenesis, including propagation of cell membrane depolarization and reversal therapies
title_full_unstemmed	A bioelectric model of carcinogenesis, including propagation of cell membrane depolarization and reversal therapies
title_sort	bioelectric model of carcinogenesis, including propagation of cell membrane depolarization and reversal therapies
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/93a4276832c143d7b6b8f4401694cc40
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A bioelectric model of carcinogenesis, including propagation of cell membrane depolarization and reversal therapies

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