Modeling triple-negative breast cancer heterogeneity: Effects of stromal macrophages, fibroblasts and tumor vasculature.

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dc.contributor.authorNorton, Kerri-Ann
dc.contributor.authorJin, Kideok
dc.contributor.authorPopel, Aleksander S
dc.contributor.orcidhttps://orcid.org/0000-0001-6898-2512
dc.date.accessioned2023-11-29T18:52:32Z
dc.date.available2023-11-29T18:52:32Z
dc.date.issued9/7/2018
dc.description.abstractA hallmark of breast tumors is its spatial heterogeneity that includes its distribution of cancer stem cells and progenitor cells, but also heterogeneity in the tumor microenvironment. In this study we focus on the contributions of stromal cells, specifically macrophages, fibroblasts, and endothelial cells on tumor progression. We develop a computational model of triple-negative breast cancer based on our previous work and expand it to include macrophage infiltration, fibroblasts, and angiogenesis. In vitro studies have shown that the secretomes of tumor-educated macrophages and fibroblasts increase both the migration and proliferation rates of triple-negative breast cancer cells. In vivo studies also demonstrated that blocking signaling of selected secreted factors inhibits tumor growth and metastasis in mouse xenograft models. We investigate the influences of increased migration and proliferation rates on tumor growth, the effect of the presence on fibroblasts or macrophages on growth and morphology, and the contributions of macrophage infiltration on tumor growth. We find that while the presence of macrophages increases overall tumor growth, the increase in macrophage infiltration does not substantially increase tumor growth and can even stifle tumor growth at excessive rates.
dc.description.grantGrant Funded
dc.description.sponsorshipR01 CA196701/CA/NCI NIH HHS/United States
dc.description.urihttps://doi.org/10.1016/j.jtbi.2018.05.003
dc.description.urihttp://www.ncbi.nlm.nih.gov/pmc/articles/pmc6127870/
dc.identifier.citationNorton KA, Jin K, Popel AS. Modeling triple-negative breast cancer heterogeneity: Effects of stromal macrophages, fibroblasts and tumor vasculature. J Theor Biol. 2018 Sep 7;452:56-68. doi: 10.1016/j.jtbi.2018.05.003. Epub 2018 May 8. PMID: 29750999; PMCID: PMC6127870.
dc.identifier.issn0022-5193
dc.identifier.other29750999
dc.identifier.urihttps://hdl.handle.net/20.500.14303/426
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofJournal of Theoretical Biology
dc.rightsThis Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). http://rightsstatements.org/vocab/InC/1.0/
dc.subjectAngiogenesis
dc.subjectCancer stem cells
dc.subjectHypoxia
dc.subjectImmune cells
dc.subjectMicroenvironment
dc.subjectTumor
dc.titleModeling triple-negative breast cancer heterogeneity: Effects of stromal macrophages, fibroblasts and tumor vasculature.
dc.typeArticle
local.departmentprogramDepartment of Pharmaceutical Sciences
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