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Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma
BACKGROUND: Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353688/ https://www.ncbi.nlm.nih.gov/pubmed/25702581 http://dx.doi.org/10.1016/j.cub.2014.12.059 |
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author | Ford, Catriona A. Petrova, Sofia Pound, John D. Voss, Jorine J.L.P. Melville, Lynsey Paterson, Margaret Farnworth, Sarah L. Gallimore, Awen M. Cuff, Simone Wheadon, Helen Dobbin, Edwina Ogden, Carol Anne Dumitriu, Ingrid E. Dunbar, Donald R. Murray, Paul G. Ruckerl, Dominik Allen, Judith E. Hume, David A. van Rooijen, Nico Goodlad, John R. Freeman, Tom C. Gregory, Christopher D. |
author_facet | Ford, Catriona A. Petrova, Sofia Pound, John D. Voss, Jorine J.L.P. Melville, Lynsey Paterson, Margaret Farnworth, Sarah L. Gallimore, Awen M. Cuff, Simone Wheadon, Helen Dobbin, Edwina Ogden, Carol Anne Dumitriu, Ingrid E. Dunbar, Donald R. Murray, Paul G. Ruckerl, Dominik Allen, Judith E. Hume, David A. van Rooijen, Nico Goodlad, John R. Freeman, Tom C. Gregory, Christopher D. |
author_sort | Ford, Catriona A. |
collection | PubMed |
description | BACKGROUND: Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. RESULTS: Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased “in situ transcriptomics” analysis—gene expression profiling of laser-captured TAMs to establish their activation signature in situ—we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. CONCLUSIONS: In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy. |
format | Online Article Text |
id | pubmed-4353688 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-43536882015-03-31 Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma Ford, Catriona A. Petrova, Sofia Pound, John D. Voss, Jorine J.L.P. Melville, Lynsey Paterson, Margaret Farnworth, Sarah L. Gallimore, Awen M. Cuff, Simone Wheadon, Helen Dobbin, Edwina Ogden, Carol Anne Dumitriu, Ingrid E. Dunbar, Donald R. Murray, Paul G. Ruckerl, Dominik Allen, Judith E. Hume, David A. van Rooijen, Nico Goodlad, John R. Freeman, Tom C. Gregory, Christopher D. Curr Biol Article BACKGROUND: Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. RESULTS: Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased “in situ transcriptomics” analysis—gene expression profiling of laser-captured TAMs to establish their activation signature in situ—we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. CONCLUSIONS: In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy. Cell Press 2015-03-02 /pmc/articles/PMC4353688/ /pubmed/25702581 http://dx.doi.org/10.1016/j.cub.2014.12.059 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ford, Catriona A. Petrova, Sofia Pound, John D. Voss, Jorine J.L.P. Melville, Lynsey Paterson, Margaret Farnworth, Sarah L. Gallimore, Awen M. Cuff, Simone Wheadon, Helen Dobbin, Edwina Ogden, Carol Anne Dumitriu, Ingrid E. Dunbar, Donald R. Murray, Paul G. Ruckerl, Dominik Allen, Judith E. Hume, David A. van Rooijen, Nico Goodlad, John R. Freeman, Tom C. Gregory, Christopher D. Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma |
title | Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma |
title_full | Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma |
title_fullStr | Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma |
title_full_unstemmed | Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma |
title_short | Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma |
title_sort | oncogenic properties of apoptotic tumor cells in aggressive b cell lymphoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353688/ https://www.ncbi.nlm.nih.gov/pubmed/25702581 http://dx.doi.org/10.1016/j.cub.2014.12.059 |
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