Microenvironmental variables need to effect intrinsic phenotypic parameters of cancer stem cells to affect tumourigenicity
- Published
- Accepted
- Subject Areas
- Mathematical Biology, Oncology, Computational Science
- Keywords
- stem cells, cancer, mathematical model, simulations, microenvironment, cancer, tumour initiating cells
- Copyright
- © 2013 Scott et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Cite this article
- 2013. Microenvironmental variables need to effect intrinsic phenotypic parameters of cancer stem cells to affect tumourigenicity. PeerJ PrePrints 1:e17v1 https://doi.org/10.7287/peerj.preprints.17v1
Abstract
Since the discovery of tumour initiating cells (TICs) in solid tumours, studies focussing on their role in cancer initiation and progression have abounded. The biological interrogation of these cells continues to yield volumes of information on their pro-tumourigenic behaviour, but actionable generalised conclusions have been scarce. Further, new information suggesting a dependence of tumour composition and growth on the microenvironment has yet to be studied theoretically. To address this point, we created a hybrid, discrete/continuous computational cellular automaton model of a generalised stem-cell driven tissue with a simple microenvironment. Using the model we explored the phenotypic traits inherent to the tumour initiating cells and the effect of the microenvironment on tissue growth. We identify the regions in phenotype parameter space where TICs are able to cause a disruption in homeostasis, leading to tissue overgrowth and tumour maintenance. As our parameters and model are non- specific, they could apply to any tissue TIC and do not assume specific genetic mutations. Targeting these phenotypic traits could represent a generalizable therapeutic strategy across cancer types. Further, we find that the microenvironmental variable does not strongly effect the outcomes, suggesting a need for direct feedback from the microenvironment onto stem-cell behaviour in future modelling endeavours.