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Blood vessel tortuosity selects against evolution of aggressive tumor cells in confined tissue environments: A modeling approach

Szabo, A; (2017) Blood vessel tortuosity selects against evolution of aggressive tumor cells in confined tissue environments: A modeling approach. PLoS Computational Biology , 13 (7) , Article e1005635. 10.1371/journal.pcbi.1005635. Green open access

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Abstract

Cancer is a disease of cellular regulation, often initiated by genetic mutation within cells, and leading to a heterogeneous cell population within tissues. In the competition for nutrients and growth space within the tumors the phenotype of each cell determines its success. Selection in this process is imposed by both the microenvironment (neighboring cells, extracellular matrix, and diffusing substances), and the whole of the organism through for example the blood supply. In this view, the development of tumor cells is in close interaction with their increasingly changing environment: the more cells can change, the more their environment will change. Furthermore, instabilities are also introduced on the organism level: blood supply can be blocked by increased tissue pressure or the tortuosity of the tumor-neovascular vessels. This coupling between cell, microenvironment, and organism results in behavior that is hard to predict. Here we introduce a cell-based computational model to study the effect of blood flow obstruction on the micro-evolution of cells within a cancerous tissue. We demonstrate that stages of tumor development emerge naturally, without the need for sequential mutation of specific genes. Secondly, we show that instabilities in blood supply can impact the overall development of tumors and lead to the extinction of the dominant aggressive phenotype, showing a clear distinction between the fitness at the cell level and survival of the population. This provides new insights into potential side effects of recent tumor vasculature normalization approaches.

Type: Article
Title: Blood vessel tortuosity selects against evolution of aggressive tumor cells in confined tissue environments: A modeling approach
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pcbi.1005635
Publisher version: http://doi.org/10.1371/journal.pcbi.1005635
Language: English
Additional information: © 2017 Szabó, Merks. 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 credited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1566560
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