Inflammation mediated metastasis: Immune induced epithelial-to-mesenchymal transition in inflammatory breast cancer cells
Genre
Journal ArticleDate
2015-07-24Author
Cohen, ENGao, H
Anfossi, S
Mego, M
Reddy, NG
Debeb, B
Giordano, A
Tin, S
Wu, Q
Garza, RJ
Cristofanilli, M
Mani, SA
Croix, DA
Ueno, NT
Woodward, WA
Luthra, R
Krishnamurthy, S
Reuben, JM
Subject
Cell Line, TumorCytokines
Epithelial-Mesenchymal Transition
Female
Humans
Inflammatory Breast Neoplasms
Neoplasm Metastasis
Neoplastic Cells, Circulating
Pilot Projects
T-Lymphocytes
Tumor Microenvironment
Permanent link to this record
http://hdl.handle.net/20.500.12613/5214
Metadata
Show full item recordDOI
10.1371/journal.pone.0132710Abstract
© 2015 Cohen et al. 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 adhesionmolecule, 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.Citation to related work
Public Library of Science (PLoS)Has part
PLoS ONEADA compliance
For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.eduae974a485f413a2113503eed53cd6c53
http://dx.doi.org/10.34944/dspace/5196