title: Inflammation Mediated Metastasis: Immune Induced Epithelial-To-Mesenchymal Transition in Inflammatory Breast Cancer Cells.
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.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Evan N
authors.initials: EN
authors.lastname: Cohen
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Simone
authors.initials: S
authors.lastname: Anfossi
authors.affiliation: National Cancer Institute, Bratislava, Slovak Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Mego
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Neelima G
authors.initials: NG
authors.lastname: Reddy
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Bisrat
authors.initials: B
authors.lastname: Debeb
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Sanda
authors.initials: S
authors.lastname: Tin
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Raul J
authors.initials: RJ
authors.lastname: Garza
authors.affiliation: Medical Oncology, Thomas Jefferson University, Philadelphia, PA, United States of America.
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Sendurai A
authors.initials: SA
authors.lastname: Mani
authors.affiliation: Roche Diagnostics, Indianapolis, IN, United States of America.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Croix
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Woodward
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Raja
authors.initials: R
authors.lastname: Luthra
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Savitri
authors.initials: S
authors.lastname: Krishnamurthy
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America; The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: James M
authors.initials: JM
authors.lastname: Reuben
mesh_terms: D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000276:immunology*; D059016:Tumor Microenvironment
chemical_list: D016207:Cytokines