Wolfe, Adam R.Trenton, Nicholaus J.Debeb, Bisrat G.Larson, RichardRuffell, BrianChu, KhoiHittelman, WalterDiehl, MichaelReuben, Jim M.Ueno, Naoto T.Woodward, Wendy A.2017-05-152017-05-152016Wolfe, 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.https://hdl.handle.net/1911/94272Inflammatory 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.engAll content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.Journal articleIL-6inflammatory breast cancermacrophagesmesenchymal stem cellsstatinshttps://doi.org/10.18632/oncotarget.12694