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Oncotarget. 2016 Dec 13;7(50):82482-82492. doi: 10.18632/oncotarget.12694.

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

Author information

1
MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
2
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
3
Department of Bioengineering, Rice University, Houston, TX, USA.
4
Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
5
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
6
Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

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.

KEYWORDS:

IL-6; inflammatory breast cancer; macrophages; mesenchymal stem cells; statins

PMID:
27756885
PMCID:
PMC5347707
DOI:
10.18632/oncotarget.12694
[Indexed for MEDLINE]
Free PMC Article

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