TY - JOUR
T1 - Inflammation mediated metastasis
T2 - Immune induced epithelial-to-mesenchymal transition in inflammatory breast cancer cells
AU - Cohen, Evan N.
AU - Gao, Hui
AU - Anfossi, Simone
AU - Mego, Michal
AU - Reddy, Neelima G.
AU - Debeb, Bisrat
AU - Giordano, Antonio
AU - Tin, Sanda
AU - Wu, Qiong
AU - Garza, Raul J.
AU - Cristofanilli, Massimo
AU - Mani, Sendurai A.
AU - Croix, Denise A.
AU - Ueno, Naoto T.
AU - Woodward, Wendy A.
AU - Luthra, Raja
AU - Krishnamurthy, Savitri
AU - Reuben, James M.
N1 - Publisher Copyright:
© 2015 Cohen et al.
PY - 2015/7/24
Y1 - 2015/7/24
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0132710
DO - 10.1371/journal.pone.0132710
M3 - Article
C2 - 26207636
AN - SCOPUS:84941624968
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 7
M1 - e0132710
ER -