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Exploring the Competition between Proliferative and Invasive Cancer Phenotypes in a Continuous Spatial Model

Tumor is characterized by extensive heterogeneity with respect to its microenvironment and its genetic composition. We extend a previously developed monoclonal continuous spatial model of tumor growth to account for polyclonal cell populations and investigate the interplay between a more proliferati...

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Autores principales: Tzamali, Eleftheria, Grekas, Georgios, Marias, Konstantinos, Sakkalis, Vangelis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123877/
https://www.ncbi.nlm.nih.gov/pubmed/25099885
http://dx.doi.org/10.1371/journal.pone.0103191
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author Tzamali, Eleftheria
Grekas, Georgios
Marias, Konstantinos
Sakkalis, Vangelis
author_facet Tzamali, Eleftheria
Grekas, Georgios
Marias, Konstantinos
Sakkalis, Vangelis
author_sort Tzamali, Eleftheria
collection PubMed
description Tumor is characterized by extensive heterogeneity with respect to its microenvironment and its genetic composition. We extend a previously developed monoclonal continuous spatial model of tumor growth to account for polyclonal cell populations and investigate the interplay between a more proliferative and a more invasive phenotype under different conditions. The model simulations demonstrate a transition from the dominance of the proliferative to the dominance of the invasive phenotype resembling malignant tumor progression and show a time period where both subpopulations are abundant. As the dominant phenotype switches from proliferative to invasive, the geometry of tumor changes from a compact and almost spherical shape to a more diffusive and fingered morphology with the proliferative phenotype to be restricted in the tumor bulk and the invasive to dominate at tumor edges. Different micro-environmental conditions and different phenotypic properties can promote or inhibit invasion demonstrating their mutual importance. The model provides a computational framework to investigate tumor heterogeneity and the constant interplay between the environment and the specific characteristics of phenotypes that should be taken into account for the prediction of tumor evolution, morphology and effective treatment.
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spelling pubmed-41238772014-08-12 Exploring the Competition between Proliferative and Invasive Cancer Phenotypes in a Continuous Spatial Model Tzamali, Eleftheria Grekas, Georgios Marias, Konstantinos Sakkalis, Vangelis PLoS One Research Article Tumor is characterized by extensive heterogeneity with respect to its microenvironment and its genetic composition. We extend a previously developed monoclonal continuous spatial model of tumor growth to account for polyclonal cell populations and investigate the interplay between a more proliferative and a more invasive phenotype under different conditions. The model simulations demonstrate a transition from the dominance of the proliferative to the dominance of the invasive phenotype resembling malignant tumor progression and show a time period where both subpopulations are abundant. As the dominant phenotype switches from proliferative to invasive, the geometry of tumor changes from a compact and almost spherical shape to a more diffusive and fingered morphology with the proliferative phenotype to be restricted in the tumor bulk and the invasive to dominate at tumor edges. Different micro-environmental conditions and different phenotypic properties can promote or inhibit invasion demonstrating their mutual importance. The model provides a computational framework to investigate tumor heterogeneity and the constant interplay between the environment and the specific characteristics of phenotypes that should be taken into account for the prediction of tumor evolution, morphology and effective treatment. Public Library of Science 2014-08-06 /pmc/articles/PMC4123877/ /pubmed/25099885 http://dx.doi.org/10.1371/journal.pone.0103191 Text en © 2014 Tzamali et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Tzamali, Eleftheria
Grekas, Georgios
Marias, Konstantinos
Sakkalis, Vangelis
Exploring the Competition between Proliferative and Invasive Cancer Phenotypes in a Continuous Spatial Model
title Exploring the Competition between Proliferative and Invasive Cancer Phenotypes in a Continuous Spatial Model
title_full Exploring the Competition between Proliferative and Invasive Cancer Phenotypes in a Continuous Spatial Model
title_fullStr Exploring the Competition between Proliferative and Invasive Cancer Phenotypes in a Continuous Spatial Model
title_full_unstemmed Exploring the Competition between Proliferative and Invasive Cancer Phenotypes in a Continuous Spatial Model
title_short Exploring the Competition between Proliferative and Invasive Cancer Phenotypes in a Continuous Spatial Model
title_sort exploring the competition between proliferative and invasive cancer phenotypes in a continuous spatial model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123877/
https://www.ncbi.nlm.nih.gov/pubmed/25099885
http://dx.doi.org/10.1371/journal.pone.0103191
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