Computational Modeling of the Crosstalk Between Macrophage Polarization and Tumor Cell Plasticity in the Tumor Microenvironment

Simple item page
dc.citation.journalTitleFrontiers in Oncology
dc.contributor.authorLi, Xuefei
dc.contributor.authorJolly, Mohit Kumar
dc.contributor.authorGeorge, Jason T.
dc.contributor.authorPienta, Kenneth J.
dc.contributor.authorLevine, Herbert
dc.date.accessioned2019-12-06T15:32:27Z
dc.date.available2019-12-06T15:32:27Z
dc.date.issued2019
dc.description.abstractTumor microenvironments contain multiple cell types interacting among one another via different signaling pathways. Furthermore, both cancer cells and different immune cells can display phenotypic plasticity in response to these communicating signals, thereby leading to complex spatiotemporal patterns that can impact therapeutic response. Here, we investigate the crosstalk between cancer cells and macrophages in a tumor microenvironment through in silico (computational) co-culture models. In particular, we investigate how macrophages of different polarization (M1 vs. M2) can interact with epithelial-mesenchymal plasticity of cancer cells, and conversely, how cancer cells exhibiting different phenotypes (epithelial vs. mesenchymal) can influence the polarization of macrophages. Based on interactions documented in the literature, an interaction network of cancer cells and macrophages is constructed. The steady states of the network are then analyzed. Various interactions were removed or added into the constructed-network to test the functions of those interactions. Also, parameters in the mathematical models were varied to explore their effects on the steady states of the network. In general, the interactions between cancer cells and macrophages can give rise to multiple stable steady-states for a given set of parameters and each steady state is stable against perturbations. Importantly, we show that the system can often reach one type of stable steady states where cancer cells go extinct. Our results may help inform efficient therapeutic strategies.
dc.identifier.citationLi, Xuefei, Jolly, Mohit Kumar, George, Jason T., et al.. "Computational Modeling of the Crosstalk Between Macrophage Polarization and Tumor Cell Plasticity in the Tumor Microenvironment." <i>Frontiers in Oncology,</i> (2019) Frontiers: https://doi.org/10.3389/fonc.2019.00010.
dc.identifier.digitalfonc-09-00010
dc.identifier.doihttps://doi.org/10.3389/fonc.2019.00010
dc.identifier.urihttps://hdl.handle.net/1911/107800
dc.language.isoeng
dc.publisherFrontiers
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleComputational Modeling of the Crosstalk Between Macrophage Polarization and Tumor Cell Plasticity in the Tumor Microenvironment
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
fonc-09-00010.pdf
Size:
1.54 MB
Format:
Adobe Portable Document Format
Download
Collections
Faculty Publications
Bioengineering Publications
Physics and Astronomy Publications