Inflammation Mediated Metastasis: Immune Induced Epithelial-To-Mesenchymal Transition in Inflammatory Breast Cancer Cells.
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 aggressi...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4514595?pdf=render |
| _version_ | 1811321098332012544 |
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| author | Evan N Cohen Hui Gao Simone Anfossi Michal Mego Neelima G Reddy Bisrat Debeb Antonio Giordano Sanda Tin Qiong Wu Raul J Garza Massimo Cristofanilli Sendurai A Mani Denise A Croix Naoto T Ueno Wendy A Woodward Raja Luthra Savitri Krishnamurthy James M Reuben |
| author_facet | Evan N Cohen Hui Gao Simone Anfossi Michal Mego Neelima G Reddy Bisrat Debeb Antonio Giordano Sanda Tin Qiong Wu Raul J Garza Massimo Cristofanilli Sendurai A Mani Denise A Croix Naoto T Ueno Wendy A Woodward Raja Luthra Savitri Krishnamurthy James M Reuben |
| author_sort | Evan N Cohen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T13:12:02Z |
| format | Article |
| id | doaj.art-748d2da440bb45ad896b1e2dbcce262d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T13:12:02Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-748d2da440bb45ad896b1e2dbcce262d2022-12-22T02:45:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01107e013271010.1371/journal.pone.0132710Inflammation Mediated Metastasis: Immune Induced Epithelial-To-Mesenchymal Transition in Inflammatory Breast Cancer Cells.Evan N CohenHui GaoSimone AnfossiMichal MegoNeelima G ReddyBisrat DebebAntonio GiordanoSanda TinQiong WuRaul J GarzaMassimo CristofanilliSendurai A ManiDenise A CroixNaoto T UenoWendy A WoodwardRaja LuthraSavitri KrishnamurthyJames M ReubenInflammatory 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.http://europepmc.org/articles/PMC4514595?pdf=render |
| spellingShingle | Evan N Cohen Hui Gao Simone Anfossi Michal Mego Neelima G Reddy Bisrat Debeb Antonio Giordano Sanda Tin Qiong Wu Raul J Garza Massimo Cristofanilli Sendurai A Mani Denise A Croix Naoto T Ueno Wendy A Woodward Raja Luthra Savitri Krishnamurthy James M Reuben Inflammation Mediated Metastasis: Immune Induced Epithelial-To-Mesenchymal Transition in Inflammatory Breast Cancer Cells. PLoS ONE |
| title | Inflammation Mediated Metastasis: Immune Induced Epithelial-To-Mesenchymal Transition in Inflammatory Breast Cancer Cells. |
| title_full | Inflammation Mediated Metastasis: Immune Induced Epithelial-To-Mesenchymal Transition in Inflammatory Breast Cancer Cells. |
| title_fullStr | Inflammation Mediated Metastasis: Immune Induced Epithelial-To-Mesenchymal Transition in Inflammatory Breast Cancer Cells. |
| title_full_unstemmed | Inflammation Mediated Metastasis: Immune Induced Epithelial-To-Mesenchymal Transition in Inflammatory Breast Cancer Cells. |
| title_short | Inflammation Mediated Metastasis: Immune Induced Epithelial-To-Mesenchymal Transition in Inflammatory Breast Cancer Cells. |
| title_sort | inflammation mediated metastasis immune induced epithelial to mesenchymal transition in inflammatory breast cancer cells |
| url | http://europepmc.org/articles/PMC4514595?pdf=render |
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