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Autocrine signaling can explain the emergence of Allee effects in cancer cell populations
In many human cancers, the rate of cell growth depends crucially on the size of the tumor cell population. Low, zero, or negative growth at low population densities is known as the Allee effect; this effect has been studied extensively in ecology, but so far lacks a good explanation in the cancer se...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923455/ https://www.ncbi.nlm.nih.gov/pubmed/35239640 http://dx.doi.org/10.1371/journal.pcbi.1009844 |
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author | Gerlee, Philip Altrock, Philipp M. Malik, Adam Krona, Cecilia Nelander, Sven |
author_facet | Gerlee, Philip Altrock, Philipp M. Malik, Adam Krona, Cecilia Nelander, Sven |
author_sort | Gerlee, Philip |
collection | PubMed |
description | In many human cancers, the rate of cell growth depends crucially on the size of the tumor cell population. Low, zero, or negative growth at low population densities is known as the Allee effect; this effect has been studied extensively in ecology, but so far lacks a good explanation in the cancer setting. Here, we formulate and analyze an individual-based model of cancer, in which cell division rates are increased by the local concentration of an autocrine growth factor produced by the cancer cells themselves. We show, analytically and by simulation, that autocrine signaling suffices to cause both strong and weak Allee effects. Whether low cell densities lead to negative (strong effect) or reduced (weak effect) growth rate depends directly on the ratio of cell death to proliferation, and indirectly on cellular dispersal. Our model is consistent with experimental observations from three patient-derived brain tumor cell lines grown at different densities. We propose that further studying and quantifying population-wide feedback, impacting cell growth, will be central for advancing our understanding of cancer dynamics and treatment, potentially exploiting Allee effects for therapy. |
format | Online Article Text |
id | pubmed-8923455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-89234552022-03-16 Autocrine signaling can explain the emergence of Allee effects in cancer cell populations Gerlee, Philip Altrock, Philipp M. Malik, Adam Krona, Cecilia Nelander, Sven PLoS Comput Biol Research Article In many human cancers, the rate of cell growth depends crucially on the size of the tumor cell population. Low, zero, or negative growth at low population densities is known as the Allee effect; this effect has been studied extensively in ecology, but so far lacks a good explanation in the cancer setting. Here, we formulate and analyze an individual-based model of cancer, in which cell division rates are increased by the local concentration of an autocrine growth factor produced by the cancer cells themselves. We show, analytically and by simulation, that autocrine signaling suffices to cause both strong and weak Allee effects. Whether low cell densities lead to negative (strong effect) or reduced (weak effect) growth rate depends directly on the ratio of cell death to proliferation, and indirectly on cellular dispersal. Our model is consistent with experimental observations from three patient-derived brain tumor cell lines grown at different densities. We propose that further studying and quantifying population-wide feedback, impacting cell growth, will be central for advancing our understanding of cancer dynamics and treatment, potentially exploiting Allee effects for therapy. Public Library of Science 2022-03-03 /pmc/articles/PMC8923455/ /pubmed/35239640 http://dx.doi.org/10.1371/journal.pcbi.1009844 Text en © 2022 Gerlee et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Gerlee, Philip Altrock, Philipp M. Malik, Adam Krona, Cecilia Nelander, Sven Autocrine signaling can explain the emergence of Allee effects in cancer cell populations |
title | Autocrine signaling can explain the emergence of Allee effects in cancer cell populations |
title_full | Autocrine signaling can explain the emergence of Allee effects in cancer cell populations |
title_fullStr | Autocrine signaling can explain the emergence of Allee effects in cancer cell populations |
title_full_unstemmed | Autocrine signaling can explain the emergence of Allee effects in cancer cell populations |
title_short | Autocrine signaling can explain the emergence of Allee effects in cancer cell populations |
title_sort | autocrine signaling can explain the emergence of allee effects in cancer cell populations |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923455/ https://www.ncbi.nlm.nih.gov/pubmed/35239640 http://dx.doi.org/10.1371/journal.pcbi.1009844 |
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