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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2015
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.
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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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