当前位置： SCI文献检索 > PLOS BIOLOGY期刊下所有文献 > Cancer cell population growth kinetics at low densities deviate from the exponential growth model and suggest an Allee effect.

Cancer cell population growth kinetics at low densities deviate from the exponential growth model and suggest an Allee effect.

Abstract：

: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.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

Johnson KE,Howard G,Mo W,Strasser MK,Lima EABF,Huang S,Brock A

doi

10.1371/journal.pbio.3000399

subject

Has Abstract

pub_date

2019-08-05 00:00:00

pages

e3000399

issue

eissn

1544-9173

issn

1545-7885

pii

PBIOLOGY-D-19-00785

journal_volume

pub_type

杂志文章

在线工具

Cancer cell population growth kinetics at low densities deviate from the exponential growth model and suggest an Allee effect.