Cancer cell population growth kinetics at low densities deviate from the exponential growth model and suggest an Allee effect.
Most models of cancer cell population expansion assume exponential growth kinetics at low cell densities, with deviations to account for observed slowing of growth rate only at higher densities due to limited resources such as space and nutrients. However, recent preclinical and clinical observation...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-08-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3000399 |
| _version_ | 1830199213582974976 |
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| author | Kaitlyn E Johnson Grant Howard William Mo Michael K Strasser Ernesto A B F Lima Sui Huang Amy Brock |
| author_facet | Kaitlyn E Johnson Grant Howard William Mo Michael K Strasser Ernesto A B F Lima Sui Huang Amy Brock |
| author_sort | Kaitlyn E Johnson |
| collection | DOAJ |
| description | Most models of cancer cell population expansion assume exponential growth kinetics at low cell densities, with deviations to account for observed slowing of growth rate only at higher densities due to limited resources such as space and nutrients. However, recent preclinical and clinical observations of tumor initiation or recurrence indicate the presence of tumor growth kinetics in which growth rates scale positively with cell numbers. These observations are analogous to the cooperative behavior of species in an ecosystem described by the ecological principle of the Allee effect. In preclinical and clinical models, however, tumor growth data are limited by the lower limit of detection (i.e., a measurable lesion) and confounding variables, such as tumor microenvironment, and immune responses may cause and mask deviations from exponential growth models. In this work, we present alternative growth models to investigate the presence of an Allee effect in cancer cells seeded at low cell densities in a controlled in vitro setting. We propose a stochastic modeling framework to disentangle expected deviations due to small population size stochastic effects from cooperative growth and use the moment approach for stochastic parameter estimation to calibrate the observed growth trajectories. We validate the framework on simulated data and apply this approach to longitudinal cell proliferation data of BT-474 luminal B breast cancer cells. We find that cell population growth kinetics are best described by a model structure that considers the Allee effect, in that the birth rate of tumor cells increases with cell number in the regime of small population size. This indicates a potentially critical role of cooperative behavior among tumor cells at low cell densities with relevance to early stage growth patterns of emerging and relapsed tumors. |
| first_indexed | 2024-12-18T02:09:32Z |
| format | Article |
| id | doaj.art-b9865c052a504627a1961fd4354b951f |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-18T02:09:32Z |
| publishDate | 2019-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-b9865c052a504627a1961fd4354b951f2022-12-21T21:24:31ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852019-08-01178e300039910.1371/journal.pbio.3000399Cancer cell population growth kinetics at low densities deviate from the exponential growth model and suggest an Allee effect.Kaitlyn E JohnsonGrant HowardWilliam MoMichael K StrasserErnesto A B F LimaSui HuangAmy BrockMost models of cancer cell population expansion assume exponential growth kinetics at low cell densities, with deviations to account for observed slowing of growth rate only at higher densities due to limited resources such as space and nutrients. However, recent preclinical and clinical observations of tumor initiation or recurrence indicate the presence of tumor growth kinetics in which growth rates scale positively with cell numbers. These observations are analogous to the cooperative behavior of species in an ecosystem described by the ecological principle of the Allee effect. In preclinical and clinical models, however, tumor growth data are limited by the lower limit of detection (i.e., a measurable lesion) and confounding variables, such as tumor microenvironment, and immune responses may cause and mask deviations from exponential growth models. In this work, we present alternative growth models to investigate the presence of an Allee effect in cancer cells seeded at low cell densities in a controlled in vitro setting. We propose a stochastic modeling framework to disentangle expected deviations due to small population size stochastic effects from cooperative growth and use the moment approach for stochastic parameter estimation to calibrate the observed growth trajectories. We validate the framework on simulated data and apply this approach to longitudinal cell proliferation data of BT-474 luminal B breast cancer cells. We find that cell population growth kinetics are best described by a model structure that considers the Allee effect, in that the birth rate of tumor cells increases with cell number in the regime of small population size. This indicates a potentially critical role of cooperative behavior among tumor cells at low cell densities with relevance to early stage growth patterns of emerging and relapsed tumors.https://doi.org/10.1371/journal.pbio.3000399 |
| spellingShingle | Kaitlyn E Johnson Grant Howard William Mo Michael K Strasser Ernesto A B F Lima Sui Huang Amy Brock Cancer cell population growth kinetics at low densities deviate from the exponential growth model and suggest an Allee effect. PLoS Biology |
| title | Cancer cell population growth kinetics at low densities deviate from the exponential growth model and suggest an Allee effect. |
| title_full | Cancer cell population growth kinetics at low densities deviate from the exponential growth model and suggest an Allee effect. |
| title_fullStr | Cancer cell population growth kinetics at low densities deviate from the exponential growth model and suggest an Allee effect. |
| title_full_unstemmed | Cancer cell population growth kinetics at low densities deviate from the exponential growth model and suggest an Allee effect. |
| title_short | Cancer cell population growth kinetics at low densities deviate from the exponential growth model and suggest an Allee effect. |
| title_sort | cancer cell population growth kinetics at low densities deviate from the exponential growth model and suggest an allee effect |
| url | https://doi.org/10.1371/journal.pbio.3000399 |
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