Abstract
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.
| Original language | English |
|---|---|
| Article number | 110677 |
| Number of pages | 14 |
| Journal | Journal of Theoretical Biology |
| Volume | 522 |
| Early online date | 27 Mar 2021 |
| DOIs | |
| Publication status | Published - 7 Aug 2021 |
Keywords
- Cancer invasion
- Organotypic assay
- Atomistic-continuum model
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Copyright © 2021 Published by Elsevier Ltd. All rights reserved. This work has been made available online in accordance with publisher policies or with permission. Permission for further reuse of this content should be sought from the publisher or the rights holder. This is the author created accepted manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1016/j.jtbi.2021.110677.