A novel 3D atomistic-continuum cancer invasion model: In silico simulations of an in vitro organotypic invasion assay.

Autor: Franssen LC; School of Mathematics and Statistics, University of St Andrews, Scotland, UK; Roche, pRED, Translational Modeling & Simulation, Basel, Switzerland. Electronic address: linneafranssen@gmail.com., Sfakianakis N; School of Mathematics and Statistics, University of St Andrews, Scotland, UK. Electronic address: n.sfakianakis@st-andrews.ac.uk., Chaplain MAJ; School of Mathematics and Statistics, University of St Andrews, Scotland, UK. Electronic address: majc@st-andrews.ac.uk.
Jazyk: angličtina
Zdroj: Journal of theoretical biology [J Theor Biol] 2021 Aug 07; Vol. 522, pp. 110677. Date of Electronic Publication: 2021 Mar 27.
DOI: 10.1016/j.jtbi.2021.110677
Abstrakt: We develop a three-dimensional genuinely hybrid atomistic-continuum model that describes the invasive growth dynamics of individual cancer cells in tissue. The framework explicitly accounts for phenotypic variation by distinguishing between cancer cells of an epithelial-like and a mesenchymal-like phenotype. It also describes mutations between these cell phenotypes in the form of epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET). The proposed model consists of a hybrid system of partial and stochastic differential equations that describe the evolution of epithelial-like and mesenchymal-like cancer cells, respectively, under the consideration of matrix-degrading enzyme concentrations and the extracellular matrix density. With the help of inverse parameter estimation and a sensitivity analysis, this three-dimensional model is then calibrated to an in vitro organotypic invasion assay experiment of oral squamous cell carcinoma cells.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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