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Autocrine signaling explains the emergence of Allee effects in cancer cell populations

Philip Gerlee, View ORCID ProfilePhilipp M. Altrock, Cecilia Krona, View ORCID ProfileSven Nelander
doi: https://doi.org/10.1101/2021.07.14.452320
Philip Gerlee
1Chalmers University of Technology & University of Gothenburg, Sweden
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Philipp M. Altrock
2Department of Integrated Mathematical Oncology, Moffitt Cancer Center, Tampa, FL 33612
3Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, 24306 Ploen, Germany
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  • For correspondence: philipp.altrock@gmail.com
Cecilia Krona
4Department of Immunology, Genetics and Pathology, Uppsala University, SE-75185 Uppsala, Sweden
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Sven Nelander
4Department of Immunology, Genetics and Pathology, Uppsala University, SE-75185 Uppsala, Sweden
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Abstract

In many human cancers, the rate of cell growth depends crucially on the size of the tumour 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 of brain tumor cells 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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* gerlee{at}chalmers.se

  • ↵† sven.nelander{at}igp.uu.se

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted July 14, 2021.
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Autocrine signaling explains the emergence of Allee effects in cancer cell populations
Philip Gerlee, Philipp M. Altrock, Cecilia Krona, Sven Nelander
bioRxiv 2021.07.14.452320; doi: https://doi.org/10.1101/2021.07.14.452320
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Autocrine signaling explains the emergence of Allee effects in cancer cell populations
Philip Gerlee, Philipp M. Altrock, Cecilia Krona, Sven Nelander
bioRxiv 2021.07.14.452320; doi: https://doi.org/10.1101/2021.07.14.452320

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