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dc.contributor.authorWolfe, Adam R.
Trenton, Nicholaus J.
Debeb, Bisrat G.
Larson, Richard
Ruffell, Brian
Chu, Khoi
Hittelman, Walter
Diehl, Michael
Reuben, Jim M.
Ueno, Naoto T.
Woodward, Wendy A.
dc.date.accessioned 2017-05-15T21:11:38Z
dc.date.available 2017-05-15T21:11:38Z
dc.date.issued 2016
dc.identifier.citation Wolfe, 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." Oncotarget, 7, (2016) 82482-82494. https://doi.org/10.18632/oncotarget.12694.
dc.identifier.urihttp://hdl.handle.net/1911/94272
dc.description.abstract Inflammatory 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.
dc.language.iso eng
dc.rights All content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/
dc.title Mesenchymal stem cells and macrophages interact through IL-6 to promote inflammatory breast cancer in pre-clinical models
dc.type Journal article
dc.citation.journalTitle Oncotarget
dc.subject.keywordIL-6
inflammatory breast cancer
macrophages
mesenchymal stem cells
statins
dc.citation.volumeNumber 7
dc.contributor.publisher Impact Journals, LLC
dc.type.dcmi Text
dc.identifier.doihttps://doi.org/10.18632/oncotarget.12694
dc.identifier.pmcid PMC5347707
dc.identifier.pmid 27756885
dc.type.publication publisher version
dc.citation.firstpage 82482
dc.citation.lastpage 82494


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