Paper Info
Title
Microenvironmental variables must influence intrinsic phenotypic parameters of cancer stem cells to affect tumourigenicity.
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 affect the outcomes, suggesting a need for direct feedback from the microenvironment onto stem-cell behaviour in future modelling endeavours.
Year
DOI
Venue
2014
10.1371/journal.pcbi.1003433
PLOS COMPUTATIONAL BIOLOGY
Keywords
DocType
Volume
algorithms,computer simulation,phenotype,mutation
Journal
10
Issue
ISSN
Citations 
1
1553-734X
4
PageRank 
References 
Authors
1.16
1
5
Name
Order
Citations
PageRank
Jacob Scott115114.00
Anita Hjelmeland241.50
Prakash Chinnaiyan341.50
Alexander R. A. Anderson43610.26
David Basanta5195.43