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Article Dans Une Revue European Physical Journal E: Soft matter and biological physics Année : 2019

Agent-based model of multicellular tumor spheroid evolution including cell metabolism

Résumé

Computational models aiming at the spatio-temporal description of cancer evolution are a suitable framework for testing biological hypotheses from experimental data, and generating new ones. Building on our recent work (J. Theor. Biol. 389, 146 (2016)) we develop a 3D agent-based model, capable of tracking hundreds of thousands of interacting cells, over time scales ranging from seconds to years. Cell dynamics is driven by a Monte Carlo solver, incorporating partial differential equations to describe chemical pathways and the activation/repression of “genes”, leading to the up- or down-regulation of specific cell markers. Each cell-agent of different kind (stem, cancer, stromal etc.) runs through its cycle, undergoes division, can exit to a dormant, senescent, necrotic state, or apoptosis, according to the inputs from its systemic network. The basic network at this stage describes glucose/oxygen/ATP cycling, and can be readily extended to cancer-cell specific markers. Eventual accumulation of chemical/radiation damage to each cell’s DNA is described by a Markov chain of internal states, and by a damage-repair network, whose evolution is linked to the cell systemic network. Aimed at a direct comparison with experiments of tumorsphere growth from stem cells, the present model will allow to quantitatively study the role of transcription factors involved in the reprogramming and variable radio-resistance of simulated cancer-stem cells, evolving in a realistic computer simulation of a growing multicellular tumorsphere.

Dates et versions

hal-03138040 , version 1 (10-02-2021)

Identifiants

Citer

Fabrizio Cleri. Agent-based model of multicellular tumor spheroid evolution including cell metabolism. European Physical Journal E: Soft matter and biological physics, 2019, 42 (8), pp.112. ⟨10.1140/epje/i2019-11878-7⟩. ⟨hal-03138040⟩
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