Modeling TGF-β in early stages of cancer tissue dynamics.

Recent works have highlighted a double role for the Transforming Growth Factor β (TGF-β): it inhibits cancer in healthy cells and potentiates tumor progression during late stage of tumorigenicity, respectively; therefore it has been termed the "Jekyll and Hyde" of cancer or, alternatively,...

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Autores principales:	Gianluca Ascolani, Pietro Liò
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3df552d9c4934f68b27645de539aeb33
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spelling	oai:doaj.org-article:3df552d9c4934f68b27645de539aeb332021-11-18T08:31:51ZModeling TGF-β in early stages of cancer tissue dynamics.1932-620310.1371/journal.pone.0088533https://doaj.org/article/3df552d9c4934f68b27645de539aeb332014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586338/?tool=EBIhttps://doaj.org/toc/1932-6203Recent works have highlighted a double role for the Transforming Growth Factor β (TGF-β): it inhibits cancer in healthy cells and potentiates tumor progression during late stage of tumorigenicity, respectively; therefore it has been termed the "Jekyll and Hyde" of cancer or, alternatively, an "excellent servant but a bad master". It remains unclear how this molecule could have the two opposite behaviours. In this work, we propose a TGF-β multi scale mathematical model at molecular, cellular and tissue scales. The multi scalar behaviours of the TGF-β are described by three coupled models built up together which can approximatively be related to distinct microscopic, mesoscopic, and macroscopic scales, respectively. We first model the dynamics of TGF-β at the single-cell level by taking into account the intracellular and extracellular balance and the autocrine and paracrine behaviour of TGF-β. Then we use the average estimates of the TGF-β from the first model to understand its dynamics in a model of duct breast tissue. Although the cellular model and the tissue model describe phenomena at different time scales, their cumulative dynamics explain the changes in the role of TGF-β in the progression from healthy to pre-tumoral to cancer. We estimate various parameters by using available gene expression datasets. Despite the fact that our model does not describe an explicit tissue geometry, it provides quantitative inference on the stage and progression of breast cancer tissue invasion that could be compared with epidemiological data in literature. Finally in the last model, we investigated the invasion of breast cancer cells in the bone niches and the subsequent disregulation of bone remodeling processes. The bone model provides an effective description of the bone dynamics in healthy and early stages cancer conditions and offers an evolutionary ecological perspective of the dynamics of the competition between cancer and healthy cells.Gianluca AscolaniPietro LiòPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e88533 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gianluca Ascolani Pietro Liò Modeling TGF-β in early stages of cancer tissue dynamics.
description	Recent works have highlighted a double role for the Transforming Growth Factor β (TGF-β): it inhibits cancer in healthy cells and potentiates tumor progression during late stage of tumorigenicity, respectively; therefore it has been termed the "Jekyll and Hyde" of cancer or, alternatively, an "excellent servant but a bad master". It remains unclear how this molecule could have the two opposite behaviours. In this work, we propose a TGF-β multi scale mathematical model at molecular, cellular and tissue scales. The multi scalar behaviours of the TGF-β are described by three coupled models built up together which can approximatively be related to distinct microscopic, mesoscopic, and macroscopic scales, respectively. We first model the dynamics of TGF-β at the single-cell level by taking into account the intracellular and extracellular balance and the autocrine and paracrine behaviour of TGF-β. Then we use the average estimates of the TGF-β from the first model to understand its dynamics in a model of duct breast tissue. Although the cellular model and the tissue model describe phenomena at different time scales, their cumulative dynamics explain the changes in the role of TGF-β in the progression from healthy to pre-tumoral to cancer. We estimate various parameters by using available gene expression datasets. Despite the fact that our model does not describe an explicit tissue geometry, it provides quantitative inference on the stage and progression of breast cancer tissue invasion that could be compared with epidemiological data in literature. Finally in the last model, we investigated the invasion of breast cancer cells in the bone niches and the subsequent disregulation of bone remodeling processes. The bone model provides an effective description of the bone dynamics in healthy and early stages cancer conditions and offers an evolutionary ecological perspective of the dynamics of the competition between cancer and healthy cells.
format	article
author	Gianluca Ascolani Pietro Liò
author_facet	Gianluca Ascolani Pietro Liò
author_sort	Gianluca Ascolani
title	Modeling TGF-β in early stages of cancer tissue dynamics.
title_short	Modeling TGF-β in early stages of cancer tissue dynamics.
title_full	Modeling TGF-β in early stages of cancer tissue dynamics.
title_fullStr	Modeling TGF-β in early stages of cancer tissue dynamics.
title_full_unstemmed	Modeling TGF-β in early stages of cancer tissue dynamics.
title_sort	modeling tgf-β in early stages of cancer tissue dynamics.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/3df552d9c4934f68b27645de539aeb33
work_keys_str_mv	AT gianlucaascolani modelingtgfbinearlystagesofcancertissuedynamics AT pietrolio modelingtgfbinearlystagesofcancertissuedynamics
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Modeling TGF-β in early stages of cancer tissue dynamics.

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