Progression of Luminal Breast Tumors Is Promoted by Ménage à Trois between the Inflammatory Cytokine TNFα and the Hormonal and Growth-Supporting Arms of the Tumor Microenvironment
Breast cancer progression is strongly linked to inflammatory processes, aggravating disease course. The impacts of the inflammatory cytokine TNFα on breast malignancy are not fully substantiated, and they may be affected by cooperativity between TNFα and other protumoral mediators. Here, we show tha...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/720536 |
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| author | Polina Weitzenfeld Nurit Meron Tal Leibovich-Rivkin Tsipi Meshel Adit Ben-Baruch |
| author_facet | Polina Weitzenfeld Nurit Meron Tal Leibovich-Rivkin Tsipi Meshel Adit Ben-Baruch |
| author_sort | Polina Weitzenfeld |
| collection | DOAJ |
| description | Breast cancer progression is strongly linked to inflammatory processes, aggravating disease course. The impacts of the inflammatory cytokine TNFα on breast malignancy are not fully substantiated, and they may be affected by cooperativity between TNFα and other protumoral mediators. Here, we show that together with representatives of other important arms of the tumor microenvironment, estrogen (hormonal) and EGF (growth-supporting), TNFα potently induced metastasis-related properties and functions in luminal breast tumor cells, representing the most common type of breast cancer. Jointly, TNFα + Estrogen + EGF had a stronger effect on breast cancer cells than each element alone, leading to the following: (1) extensive cell spreading and formation of FAK/paxillin-enriched cellular protrusions; (2) elevated proportion of tumor cells coexpressing high levels of CD44 and β1 and VLA6; (3) EMT and cell migration; (4) resistance to chemotherapy; (5) release of protumoral factors (CXCL8, CCL2, MMPs). Importantly, the tumor cells used in this study are known to be nonmetastatic under all conditions; nevertheless, they have acquired high metastasizing abilities in vivo in mice, following a brief stimulation by TNFα + Estrogen + EGF. These dramatic findings indicate that TNFα can turn into a strong prometastatic factor, suggesting a paradigm shift in which clinically approved inhibitors of TNFα would be applied in breast cancer therapy. |
| format | Article |
| id | doaj-art-b9e9da7511a14c49a4088279e9ac5eda |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-b9e9da7511a14c49a4088279e9ac5eda2025-02-03T05:57:47ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/720536720536Progression of Luminal Breast Tumors Is Promoted by Ménage à Trois between the Inflammatory Cytokine TNFα and the Hormonal and Growth-Supporting Arms of the Tumor MicroenvironmentPolina Weitzenfeld0Nurit Meron1Tal Leibovich-Rivkin2Tsipi Meshel3Adit Ben-Baruch4Ela Kodesz Institute for Research on Cancer Development and Prevention, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, IsraelEla Kodesz Institute for Research on Cancer Development and Prevention, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, IsraelEla Kodesz Institute for Research on Cancer Development and Prevention, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, IsraelEla Kodesz Institute for Research on Cancer Development and Prevention, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, IsraelEla Kodesz Institute for Research on Cancer Development and Prevention, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, IsraelBreast cancer progression is strongly linked to inflammatory processes, aggravating disease course. The impacts of the inflammatory cytokine TNFα on breast malignancy are not fully substantiated, and they may be affected by cooperativity between TNFα and other protumoral mediators. Here, we show that together with representatives of other important arms of the tumor microenvironment, estrogen (hormonal) and EGF (growth-supporting), TNFα potently induced metastasis-related properties and functions in luminal breast tumor cells, representing the most common type of breast cancer. Jointly, TNFα + Estrogen + EGF had a stronger effect on breast cancer cells than each element alone, leading to the following: (1) extensive cell spreading and formation of FAK/paxillin-enriched cellular protrusions; (2) elevated proportion of tumor cells coexpressing high levels of CD44 and β1 and VLA6; (3) EMT and cell migration; (4) resistance to chemotherapy; (5) release of protumoral factors (CXCL8, CCL2, MMPs). Importantly, the tumor cells used in this study are known to be nonmetastatic under all conditions; nevertheless, they have acquired high metastasizing abilities in vivo in mice, following a brief stimulation by TNFα + Estrogen + EGF. These dramatic findings indicate that TNFα can turn into a strong prometastatic factor, suggesting a paradigm shift in which clinically approved inhibitors of TNFα would be applied in breast cancer therapy.http://dx.doi.org/10.1155/2013/720536 |
| spellingShingle | Polina Weitzenfeld Nurit Meron Tal Leibovich-Rivkin Tsipi Meshel Adit Ben-Baruch Progression of Luminal Breast Tumors Is Promoted by Ménage à Trois between the Inflammatory Cytokine TNFα and the Hormonal and Growth-Supporting Arms of the Tumor Microenvironment Mediators of Inflammation |
| title | Progression of Luminal Breast Tumors Is Promoted by Ménage à Trois between the Inflammatory Cytokine TNFα and the Hormonal and Growth-Supporting Arms of the Tumor Microenvironment |
| title_full | Progression of Luminal Breast Tumors Is Promoted by Ménage à Trois between the Inflammatory Cytokine TNFα and the Hormonal and Growth-Supporting Arms of the Tumor Microenvironment |
| title_fullStr | Progression of Luminal Breast Tumors Is Promoted by Ménage à Trois between the Inflammatory Cytokine TNFα and the Hormonal and Growth-Supporting Arms of the Tumor Microenvironment |
| title_full_unstemmed | Progression of Luminal Breast Tumors Is Promoted by Ménage à Trois between the Inflammatory Cytokine TNFα and the Hormonal and Growth-Supporting Arms of the Tumor Microenvironment |
| title_short | Progression of Luminal Breast Tumors Is Promoted by Ménage à Trois between the Inflammatory Cytokine TNFα and the Hormonal and Growth-Supporting Arms of the Tumor Microenvironment |
| title_sort | progression of luminal breast tumors is promoted by menage a trois between the inflammatory cytokine tnfα and the hormonal and growth supporting arms of the tumor microenvironment |
| url | http://dx.doi.org/10.1155/2013/720536 |
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