Mesenchymal stem cells and macrophages interact through IL-6 to promote inflammatory breast cancer in pre-clinical models

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dc.citation.firstpage82482en_US
dc.citation.journalTitleOncotargeten_US
dc.citation.lastpage82494en_US
dc.citation.volumeNumber7en_US
dc.contributor.authorWolfe, Adam R.en_US
dc.contributor.authorTrenton, Nicholaus J.en_US
dc.contributor.authorDebeb, Bisrat G.en_US
dc.contributor.authorLarson, Richarden_US
dc.contributor.authorRuffell, Brianen_US
dc.contributor.authorChu, Khoien_US
dc.contributor.authorHittelman, Walteren_US
dc.contributor.authorDiehl, Michaelen_US
dc.contributor.authorReuben, Jim M.en_US
dc.contributor.authorUeno, Naoto T.en_US
dc.contributor.authorWoodward, Wendy A.en_US
dc.date.accessioned2017-05-15T21:11:38Zen_US
dc.date.available2017-05-15T21:11:38Zen_US
dc.date.issued2016en_US
dc.description.abstractInflammatory breast cancer (IBC) is a unique and deadly disease with unknown drivers. We hypothesized the inflammatory environment contributes to the IBC phenotype. We used an in vitro co-culture system to investigate interactions between normal and polarized macrophages (RAW 264.7 cell line), bone-marrow derived mesenchymal stem cells (MSCs), and IBC cells (SUM 149 and MDA-IBC3). We used an in vivo model that reproduces the IBC phenotype by co-injecting IBC cells with MSCs into the mammary fat pad. Mice were then treated with a macrophage recruitment inhibitor, anti-CSF1. MSC and macrophages grown in co-culture produced higher levels of pro-tumor properties such as enhanced migration and elevated IL-6 secretion. IBC cells co-cultured with educated MSCs also displayed enhanced invasion and mammosphere formation and blocked by anti-IL-6 and statin treatment. The treatment of mice co-injected with IBC cells and MSCs with anti-CSF1 inhibited tumor associated macrophages and inhibited pSTAT3 expression in tumor cells. Anti-CSF1 treated mice also exhibited reduced tumor growth, skin invasion, and local recurrence. Herein we demonstrate reciprocal tumor interactions through IL-6 with cells found in the IBC microenvironment. Our results suggest IL-6 is a mediator of these tumor promoting influences and is important for the IBC induced migration of MSCs.en_US
dc.identifier.citationWolfe, Adam R., Trenton, Nicholaus J., Debeb, Bisrat G., et al.. "Mesenchymal stem cells and macrophages interact through IL-6 to promote inflammatory breast cancer in pre-clinical models." <i>Oncotarget,</i> 7, (2016) Impact Journals, LLC: 82482-82494. https://doi.org/10.18632/oncotarget.12694.en_US
dc.identifier.doihttps://doi.org/10.18632/oncotarget.12694en_US
dc.identifier.urihttps://hdl.handle.net/1911/94272en_US
dc.language.isoengen_US
dc.publisherImpact Journals, LLCen_US
dc.rightsAll content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/en_US
dc.subject.keywordIL-6en_US
dc.subject.keywordinflammatory breast canceren_US
dc.subject.keywordmacrophagesen_US
dc.subject.keywordmesenchymal stem cellsen_US
dc.subject.keywordstatinsen_US
dc.titleMesenchymal stem cells and macrophages interact through IL-6 to promote inflammatory breast cancer in pre-clinical modelsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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