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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-03-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009844&type=printable |
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| author | Philip Gerlee Philipp M Altrock Adam Malik Cecilia Krona Sven Nelander |
| author_facet | Philip Gerlee Philipp M Altrock Adam Malik Cecilia Krona Sven Nelander |
| author_sort | Philip Gerlee |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-e0f7c0e08e3b4820bf9811e8e9bce0c8 |
| institution | DOAJ |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2022-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-e0f7c0e08e3b4820bf9811e8e9bce0c82025-08-20T02:46:24ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582022-03-01183e100984410.1371/journal.pcbi.1009844Autocrine signaling can explain the emergence of Allee effects in cancer cell populations.Philip GerleePhilipp M AltrockAdam MalikCecilia KronaSven NelanderIn 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.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009844&type=printable |
| spellingShingle | Philip Gerlee Philipp M Altrock Adam Malik Cecilia Krona Sven Nelander Autocrine signaling can explain the emergence of Allee effects in cancer cell populations. PLoS Computational Biology |
| 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 |
| url | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009844&type=printable |
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