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Oncogenic properties of apoptotic tumor cells in aggressive B cell lymphoma.

Ford, CA; Petrova, S; Pound, JD; Voss, JJ; Melville, L; Paterson, M; Farnworth, SL; Gallimore, AM; Cuff, S; Wheadon, H; et al. Ford, CA; Petrova, S; Pound, JD; Voss, JJ; Melville, L; Paterson, M; Farnworth, SL; Gallimore, AM; Cuff, S; Wheadon, H; Dobbin, E; Ogden, CA; Dumitriu, IE; Dunbar, DR; Murray, PG; Ruckerl, D; Allen, JE; Hume, DA; van Rooijen, N; Goodlad, JR; Freeman, TC; Gregory, CD (2015) Oncogenic properties of apoptotic tumor cells in aggressive B cell lymphoma. Current Biology, 25 (5). pp. 577-588. https://doi.org/10.1016/j.cub.2014.12.059
SGUL Authors: Dumitriu, Ingrid Elena

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Abstract

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.

Item Type: Article
Additional Information: Copyright © 2015 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Keywords: Developmental Biology, 06 Biological Sciences, 11 Medical And Health Sciences, 17 Psychology And Cognitive Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cardiac (INCCCA)
Journal or Publication Title: Current Biology
Language: eng
Dates:
DateEvent
2 March 2015Published
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
UNSPECIFIEDBiotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
UNSPECIFIEDBritish Heart Foundationhttp://dx.doi.org/10.13039/501100000274
PubMed ID: 25702581
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107475
Publisher's version: https://doi.org/10.1016/j.cub.2014.12.059

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