Evan N Cohen, Department of Hematopathology, University of Texas MD Anderson Cancer Center; Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center; University of Texas MD Anderson Cancer Center, University of Texas Graduate School of Biomedical Sciences at HoustonFollow
Hui Gao, Department of Hematopathology, University of Texas MD Anderson Cancer Center; Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer CenterFollow
Simone Anfossi, Department of Hematopathology, University of Texas MD Anderson Cancer Center; Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center; University of Texas MD Anderson Cancer Center, University of Texas Graduate School of Biomedical Sciences at HoustonFollow
Michal Mego, National Cancer Institute, Bratislava, Slovakia
Neelima G Reddy, Department of Hematopathology, University of Texas MD Anderson Cancer Center
Bisrat Debeb, Department of Radiation Oncology, University of Texas MD Anderson Cancer Center; Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center
Antonio Giordano, Department of Hematopathology, University of Texas MD Anderson Cancer Center; Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer CenterFollow
Sanda Tin, Department of Hematopathology, University of Texas MD Anderson Cancer Center; Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center; University of Texas MD Anderson Cancer Center, University of Texas Graduate School of Biomedical Sciences at Houston
Qiong Wu, Department of Hematopathology, University of Texas MD Anderson Cancer Center; Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center
Raul J Garza, Department of Hematopathology, University of Texas MD Anderson Cancer Center; Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center
Massimo Cristofanilli, Medical Oncology, Thomas Jefferson UniversityFollow
Sendurai A Mani, Department of Pathology, University of Texas MD Anderson Cancer Center; University of Texas MD Anderson Cancer Center, University of Texas Graduate School of Biomedical Sciences at HoustonFollow
Denise A Croix, Roche Diagnostics, Indianapolis, IN
Naoto T Ueno, Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center; Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center; University of Texas MD Anderson Cancer Center, University of Texas Graduate School of Biomedical Sciences at HoustonFollow
Wendy A Woodward, Department of Radiation Oncology, University of Texas MD Anderson Cancer Center; Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center; University of Texas MD Anderson Cancer Center, University of Texas Graduate School of Biomedical Sciences at HoustonFollow
Raja Luthra, Department of Hematopathology, University of Texas MD Anderson Cancer Center
Savitri Krishnamurthy, Department of Pathology, University of Texas MD Anderson Cancer Center; Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center
James M Reuben, Department of Hematopathology, University of Texas MD Anderson Cancer Center; Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center; University of Texas MD Anderson Cancer Center, University of Texas Graduate School of Biomedical Sciences at HoustonFollow

Document Type

Article

Publication Date

7-24-2015

Comments

This article has been peer reviewed. It was published in: PLoS ONE.
Volume 10, Issue 7, 24 July 2015, Article number e0132710.
The published version is available at DOI: 10.1371/journal.pone.0132710

Copyright © 2015 Cohen et al.

Abstract

Inflammatory breast cancer (IBC) is the most insidious form of locally advanced breast cancer; about a third of patients have distant metastasis at initial staging. Emerging evidence suggests that host factors in the tumor microenvironment may interact with underlying IBC cells to make them aggressive. It is unknown whether immune cells associated to the IBC microenvironment play a role in this scenario to transiently promote epithelial to mesenchymal transition (EMT) in these cells. We hypothesized that soluble factors secreted by activated immune cells can induce an EMT in IBC and thus promote metastasis. In a pilot study of 16 breast cancer patients, TNF-α production by peripheral blood T cells was correlated with the detection of circulating tumor cells expressing EMT markers. In a variety of IBC model cell lines, soluble factors from activated T cells induced expression of EMT-related genes, including FN1, VIM, TGM2, ZEB1. Interestingly, although IBC cells exhibited increased invasion and migration following exposure to immune factors, the expression of E-cadherin (CDH1), a cell adhesion molecule, increased uniquely in IBC cell lines but not in non-IBC cell lines. A combination of TNF-α, IL-6, and TGF-β was able to recapitulate EMT induction in IBC, and conditioned media preloaded with neutralizing antibodies against these factors exhibited decreased EMT. These data suggest that release of cytokines by activated immune cells may contribute to the aggressiveness of IBC and highlight these factors as potential target mediators of immune-IBC interaction.

PubMed ID

26207636

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