Cancer cell population growth kinetics at low densities deviate from the exponential growth model and suggest an Allee effect.
Journal
PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
19
03
2019
accepted:
08
07
2019
revised:
15
08
2019
pubmed:
6
8
2019
medline:
28
2
2020
entrez:
6
8
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31381560
doi: 10.1371/journal.pbio.3000399
pii: PBIOLOGY-D-19-00785
pmc: PMC6695196
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3000399Subventions
Organisme : NCI NIH HHS
ID : R01 CA226258
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA174706
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA186193
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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