Biomedical Engineering Reference
In-Depth Information
Modeling Heterogeneous Tumor Growth
Using Hybrid Cellular Automata
Sachin Man Bajimaya Shrestha, Grand Joldes, Adam Wittek,
and Karol Miller
Abstract We show that heterogeneity of cells that compose a tumor leads to its
irregular growth. We model avascular tumor growth using cellular automata (CA).
In our model, we take into account the composition of cells and intercellular
adhesion in addition to processes involved in cell cycle—proliferation, quiescence,
apoptosis and necrosis. More importantly, we consider cell mutation that gives rise
to a different phenotype and therefore, a tumor with heterogeneous population of
cells. A new phenotype is probabilistically chosen and has the ability to survive at
lower levels of nutrient concentration and reproduce faster. We solve diffusion
equation using central difference method to determine the concentration of
nutrients, in particular, oxygen available to each cell during the growth process.
We present the growth simulation and demonstrate similarity with theoretical
findings.
1
Introduction
Tumor growth is a multistage process. Mutations in a single normal cell lead to loss
of its homeostatic mechanism which is the fundamental regulatory mechanism of
cells. This leads to inappropriate mitosis (cell division) and loss of apoptosis, a
process by which cells die after exceeding their natural lifespan [
1
]. The normal cell
thus transforms to a cancerous cell. The cell proliferates unregulated and gives rise
to a heterogeneous irregular tumor growth. The size of initial growth is dependent
on the supply of nutrients, in particular, oxygen, through diffusion [
2
] and this
initial phase is called the avascular growth phase. Once tumor reaches the diffusion-
limited size, it has to recruit blood vessels to supply it with further nutrients.
S.M.B. Shrestha (
*
) G. Joldes A. Wittek K. Miller
Intelligent Systems for Medicine Laboratory, School of Mechanical
and Chemical Engineering, The University of Western Australia, Crawley 6009, WA, Australia
e-mail:
shress02@mech.uwa.edu.au
