Journal Article

FZJ-2023-01762

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Multiscale Modeling of Spheroid Tumors: Effect of Nutrient Availability on Tumor Evolution

Rosenbauer, J.FZJ* ; Berghoff, M. ; Glazier, J. A. ; Schug, A. (Corresponding author)FZJ*

2023
Soc. Washington, DC

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Please use a persistent id in citations: http://hdl.handle.net/2128/34364  doi:10.1021/acs.jpcb.2c08114

Abstract: Recent years have revealed a large number of complex mechanisms and interactions that drive the development of malignant tumors. Tumor evolution is a framework that explains tumor development as a process driven by survival of the fittest, with tumor cells of different properties competing for limited available resources. To predict the evolutionary trajectory of a tumor, knowledge of how cellular properties influence the fitness of a subpopulation in the context of the microenvironment is required and is often inaccessible. Computational multiscale-modeling of tissues enables the observation of the full trajectory of each cell within the tumor environment. Here, we model a 3D spheroid tumor with subcellular resolution. The fitness of individual cells and the evolutionary behavior of the tumor are quantified and linked to cellular and environmental parameters. The fitness of cells is solely influenced by their position in the tumor, which in turn is influenced by the two variable parameters of our model: cell–cell adhesion and cell motility. We observe the influence of nutrient independence and static and dynamically changing nutrient availability on the evolutionary trajectories of heterogeneous tumors in a high-resolution computational model. Regardless of nutrient availability, we find a fitness advantage of low-adhesion cells, which are favorable for tumor invasion. We find that the introduction of nutrient-dependent cell division and death accelerates the evolutionary speed. The evolutionary speed can be increased by fluctuations in nutrients. We identify a distinct frequency domain in which the evolutionary speed increases significantly over a tumor with constant nutrient supply. The findings suggest that an unstable supply of nutrients can accelerate tumor evolution and, thus, the transition to malignancy.

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Contributing Institute(s):

1. Jülich Supercomputing Center (JSC)

Research Program(s):

1. 5111 - Domain-Specific Simulation & Data Life Cycle Labs (SDLs) and Research Groups (POF4-511) (POF4-511)
2. Forschergruppe Schug (hkf6_20200501) (hkf6_20200501)

Appears in the scientific report 2023

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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