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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...

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Autores principales: Gerlee, Philip, Altrock, Philipp M., Malik, Adam, Krona, Cecilia, Nelander, Sven
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
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.
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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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