dorsal/arxiv
View SchemaSimulating the Impact of a Molecular 'Decision-Process' on Cellular Phenotype and Multicellular Patterns in Brain Tumors
| Authors | Chaitanya Athale, Yuri Mansury, Thomas S. Deisboeck |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0408001 |
| URL | https://arxiv.org/abs/q-bio/0408001 |
| DOI | 10.1016/j.jtbi.2004.10.019 |
| Journal | Journal of Theoretical Biology, Vol. 233, Issue 4 , 21 April 2005, Pages 469-481 |
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.
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"abstract": "Experimental evidence indicates that human brain cancer cells proliferate or\nmigrate, yet do not display both phenotypes at the same time. Here, we present\na novel computational model simulating this cellular decision-process leading\nup to either phenotype based on a molecular interaction network of genes and\nproteins. The model\u0027s regulatory network consists of the epidermal growth\nfactor receptor (EGFR), its ligand transforming growth factor-a (TGFa), the\ndownstream enzyme phospholipaseC-gamma (PLCg) and a mitosis-associated response\npathway. This network is activated by autocrine TGFa secretion, and the\nEGFR-dependent downstream signaling this step triggers, as well as modulated by\nan extrinsic nutritive glucose gradient. Employing a framework of mass action\nkinetics within a multiscale agent-based environment, we analyze both the\nemergent multicellular behavior of tumor growth and the single-cell molecular\nprofiles that change over time and space. Our results show that one can indeed\nsimulate the dichotomy between cell migration and proliferation based solely on\nan EGFR decision network. It turns out that these behavioral decisions on the\nsingle cell level impact the spatial dynamics of the entire cancerous system.\nFurthermore, the simulation results yield intriguing experimentally testable\nhypotheses also on the sub-cellular level such as spatial cytosolic\npolarization of PLCg towards an extrinsic chemotactic gradient. Implications of\nthese results for future works, both on the modeling and experimental side are\ndiscussed.",
"arxiv_id": "q-bio/0408001",
"authors": [
"Chaitanya Athale",
"Yuri Mansury",
"Thomas S. Deisboeck"
],
"categories": [
"q-bio.CB"
],
"doi": "10.1016/j.jtbi.2004.10.019",
"journal_ref": "Journal of Theoretical Biology, Vol. 233, Issue 4 , 21 April 2005,\n Pages 469-481",
"title": "Simulating the Impact of a Molecular \u0027Decision-Process\u0027 on Cellular Phenotype and Multicellular Patterns in Brain Tumors",
"url": "https://arxiv.org/abs/q-bio/0408001"
},
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