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

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. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

A three-dimensional hybrid atomistic-continuum model is developed to describe the invasive growth dynamics of individual cancer cells in tissue, accounting for phenotypic variation and transitions between epithelial-like and mesenchymal-like cell phenotypes. The model consists of partial and stochastic differential equations considering matrix-degrading enzyme concentrations and extracellular matrix density, calibrated to an in vitro invasion assay experiment of oral squamous cell carcinoma cells through parameter estimation and sensitivity analysis. This model provides a new theoretical basis for studying the invasion mechanisms of cancer cells.