Capturing the dynamics of a hybrid multiscale cancer model with a continuum model

Joshi, Tanvi V.; Avitabile, Daniele; Owen, Markus R.

Abstract

Cancer is a complex disease involving processes at spatial scales from sub-cellular, like cell signalling, to tissue scale, such as vascular network formation. A number of multiscale models have been developed to study the dynamics that emerge from the coupling between the intracellular, cellular and tissue scales. Here, we develop a continuum partial differential equation model to capture the dynamics of a particular multiscale model (a hybrid cellular automaton with discrete cells, diffusible factors and an explicit vascular network). The purpose is to test under which circumstances such a continuum model gives equivalent predictions to the original multi-scale model, in the knowledge that the system details are known, and differences in model results can be explained in terms of model features (rather than unknown experimental confounding factors). The continuum model qualitatively replicates the dynamics from the multiscale model, with certain discrepancies observed owing to the differences in the modelling of certain processes. The continuum model admits travelling wave solutions for normal tissue growth and tumour invasion, with similar behaviour observed in the multiscale model. However, the continuum model enables us to analyse the spatially homogeneous steady states of the system, and hence to analyse these waves in more detail. We show that the tumour microenvironmental effects from the multiscale model mean that tumour invasion exhibits a so-called pushed wave when the carrying capacity for tumour cell proliferation is less than the total cell density at the tumour wave front. These pushed waves of tumour invasion propagate by triggering apoptosis of normal cells at the wave front. Otherwise, numerical evidence suggests that the wave speed can be predicted from linear analysis about the normal tissue steady state.

Citation

Joshi, T. V., Avitabile, D., & Owen, M. R. (2018). Capturing the dynamics of a hybrid multiscale cancer model with a continuum model. Bulletin of Mathematical Biology, 80(6), 1435–1475. https://doi.org/10.1007/s11538-018-0406-6

• Journal Article Type: Article
• Acceptance Date: Feb 9, 2018
• Online Publication Date: Mar 16, 2018
• Publication Date: Jun 30, 2018
• Deposit Date: Feb 12, 2018
• Publicly Available Date: Mar 17, 2019
• Journal: Bulletin of Mathematical Biology
• Print ISSN: 0092-8240
• Electronic ISSN: 1522-9602
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 80
• Issue: 6
• Pages: 1435–1475
• DOI: https://doi.org/10.1007/s11538-018-0406-6
• Keywords: Multiscale; Continuum; Wave speed; Pushed waves
• Public URL: https://nottingham-repository.worktribe.com/output/944060
• Publisher URL: https://link.springer.com/article/10.1007/s11538-018-0406-6
• Additional Information: This is a post-peer-review, pre-copyedit version of an article published in Bulletin of Mathematical Biology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s11538-018-0406-6.
• Contract Date: Feb 12, 2018