Abstract
Purpose
To develop an on-lattice agent-based model describing the growth of multicellular
tumor spheroids using simple Monte Carlo tools.
Methods
Cells are situated on the vertices of a cubic grid. Different cell states (proliferative,
hypoxic or dead) and cell evolution rules, driven by 10 parameters, and the effects
of the culture medium are included. About twenty spheroids of MCF-7 human breast cancer
were cultivated and the experimental data were used for tuning the model parameters.
Results
Simulated spheroids showed adequate sizes of the necrotic nuclei and of the hypoxic
and proliferative cell phases as a function of the growth time, mimicking the overall
characteristics of the experimental spheroids. The relation between the radii of the
necrotic nucleus and the whole spheroid obtained in the simulations was similar to
the experimental one and the number of cells, as a function of the spheroid volume,
was well reproduced. The statistical variability of the Monte Carlo model described
the whole volume range observed for the experimental spheroids. Assuming that the
model parameters vary within Gaussian distributions it was obtained a sample of spheroids
that reproduced much better the experimental findings.
Conclusions
The model developed allows describing the growth of in vitro multicellular spheroids and the experimental variability can be well reproduced.
Its flexibility permits to vary both the agents involved and the rules that govern
the spheroid growth. More general situations, such as, e. g., tumor vascularization, radiotherapy effects on solid tumors, or the validity of
the tumor growth mathematical models can be studied.
Keywords
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Article info
Publication history
Published online: September 01, 2020
Accepted:
July 19,
2020
Received:
March 23,
2020
Footnotes
☆This work is part of the Ph. D. thesis developed by S. Ruiz-Arrebola within the Ph. D. program “Clinical Medicine and Public Health” at the University of Granada.
Identification
Copyright
© 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
