Microenvironmental variables must influence intrinsic phenotypic parameters of cancer stem cells to affect tumourigenicity.
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.
Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America ; Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, United Kingdom.
Jacob G
JG
Scott
Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Anita B
AB
Hjelmeland
Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.
Prakash
P
Chinnaiyan
Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.
Alexander R A
AR
Anderson
Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.
David
D
Basanta
D000465:Algorithms; D001921:Brain / Q000473:pathology*; D015687:Cell Hypoxia; D002471:Cell Transformation, Neoplastic; D003198:Computer Simulation; D018450:Disease Progression; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000503:physiopathology*; D014411:Neoplastic Stem Cells / Q000166:cytology*; D010641:Phenotype; D059016:Tumor Microenvironment