Simulating the impact of a molecular `decision-process' on cellular phenotype and multicellular patterns in brain tumors
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Publication:781256
DOI10.1016/J.JTBI.2004.10.019zbMATH Open1443.92076arXivq-bio/0408001OpenAlexW1974034376WikidataQ40440655 ScholiaQ40440655MaRDI QIDQ781256FDOQ781256
Authors: Yuri Mansury, Thomas S. Deisboeck, Chaitanya A. Athale 
Publication date: 16 July 2020
Published in: Journal of Theoretical Biology (Search for Journal in Brave)
Abstract: Experimental evidence indicates that human brain cancer cells proliferate or migrate, yet do not display both phenotypes at the same time. Here, we present a novel computational model simulating this cellular decision-process leading up to either phenotype based on a molecular interaction network of genes and proteins. The model's regulatory network consists of the epidermal growth factor receptor (EGFR), its ligand transforming growth factor-a (TGFa), the downstream enzyme phospholipaseC-gamma (PLCg) and a mitosis-associated response pathway. This network is activated by autocrine TGFa secretion, and the EGFR-dependent downstream signaling this step triggers, as well as modulated by an extrinsic nutritive glucose gradient. Employing a framework of mass action kinetics within a multiscale agent-based environment, we analyze both the emergent multicellular behavior of tumor growth and the single-cell molecular profiles that change over time and space. Our results show that one can indeed simulate the dichotomy between cell migration and proliferation based solely on an EGFR decision network. It turns out that these behavioral decisions on the single cell level impact the spatial dynamics of the entire cancerous system. Furthermore, the simulation results yield intriguing experimentally testable hypotheses also on the sub-cellular level such as spatial cytosolic polarization of PLCg towards an extrinsic chemotactic gradient. Implications of these results for future works, both on the modeling and experimental side are discussed.
Full work available at URL: https://arxiv.org/abs/q-bio/0408001
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Cites Work
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Cited In (16)
- The impact of ``search precision in an agent-based tumor model
- Density-dependent quiescence in glioma invasion: instability in a simple reaction–diffusion model for the migration/proliferation dichotomy
- A hybrid three-scale model of tumor growth
- The effects of EGF-receptor density on multiscale tumor growth patterns
- Development of a three-dimensional multiscale agent-based tumor model: simulating gene-protein interaction profiles, cell phenotypes and multicellular patterns in brain cancer
- An integrated agent-mathematical model of the effect of intercellular signalling via the epidermal growth factor receptor on cell proliferation
- Simulating brain tumor heterogeneity with a multiscale agent-based model: Linking molecular signatures, phenotypes and expansion rate
- An \textit{in silico} model to demonstrate the effects of Maspin on cancer cell dynamics
- Multi-scale, multi-resolution brain cancer modeling
- Mathematical model and its fast numerical method for the tumor growth
- A coupled mass transport and deformation theory of multi-constituent tumor growth
- Novel 3D \textit{GPU} based numerical parallel diffusion algorithms in cylindrical coordinates for health care simulation
- On simulating the generation of mosaicism during mammalian cerebral cortical development
- A process algebra framework for multi-scale modelling of biological systems
- A branching process model of heterogeneous DNA damages caused by radiotherapy in \textit{in vitro} cell cultures
- Simulating the time series of a selected gene expression profile in an agent-based tumor model
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