The non-targeted effects of radiation are perpetuated by exosomes

Al-Mayah, Ammar H. J.; Bright, Scott J.; Chapman, Kim; Irons, Sarah L.; Luo, Ping; Carter, David; Goodwin, Edwin H.; Kadhim, Munira

doi:10.1016/j.mrfmmm.2014.12.007

Cited by 142 publications

(146 citation statements)

References 48 publications

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“…Our recent work showed that EVs mediate BE following irradiation (48,67). Subsequent findings have confirmed that EVs mediate BE following different stresses, including radiation (48,49,67) and heat shock (59).…”

Section: Cisplatin Evs Can Cause Bystander Effect and An Adaptive Resmentioning

confidence: 53%

Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells

Samuel

Mulcahy

Furlong

et al. 2017

Phil. Trans. R. Soc. B

105

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Ovarian cancer has a poor overall survival that is partly caused by resistance to drugs such as cisplatin. Resistance can be acquired as a result of changes to the tumour or due to altered interactions within the tumour microenvironment. Extracellular vesicles (EVs), small lipid-bound vesicles that are loaded with macromolecular cargo and released by cells, are emerging as mediators of communication in the tumour microenvironment. We previously showed that EVs mediate the bystander effect, a phenomenon in which stressed cells can communicate with neighbouring naive cells leading to various effects including DNA damage; however, the role of EVs released following cisplatin treatment has not been tested. Here we show that treatment of cells with cisplatin led to the release of EVs that could induce invasion and increased resistance when taken up by bystander cells. This coincided with changes in p38 and JNK signalling, suggesting that these pathways may be involved in mediating the effects. We also show that EV uptake inhibitors could prevent this EV-mediated adaptive response and thus sensitize cells in vitro to the effects of cisplatin. Our results suggest that preventing pro-tumourigenic EV cross-talk during chemotherapy is a potential therapeutic target for improving outcome in ovarian cancer patients. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.

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Section: Cisplatin Evs Can Cause Bystander Effect and An Adaptive Resmentioning

confidence: 53%

Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells

Samuel

Mulcahy

Furlong

et al. 2017

Phil. Trans. R. Soc. B

105

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show abstract

“…Their exchange between cancer and nearby cells induces the 'cancer field effect', by influencing the phenotype of recipient cells towards induction of oncogenic properties (24). Exosomes released from 2 Gy-irradiated cells mediate RIBE in in vitro media-transfer experiments, manifested as induction of DNA damage and chromosome aberrations in naïve bystander cells (25,26).…”

Section: Analysis Of Exosomesmentioning

confidence: 99%

Radiotherapy for Non–Small Cell Lung Cancer Induces DNA Damage Response in Both Irradiated and Out-of-field Normal Tissues

Siva

Lobachevsky

MacManus

et al. 2016

Clinical Cancer Research

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“…Knowledge of UV’s modulatory effect upon exosome function is promising as it may provide a point of reconciliation between the UV-mediated bystander effect and the previously discussed soluble factor-mediated bystander effect. To elaborate, exosomes are extracellular vesicles derived from pinched off sections of the endosomal membrane [29]. These 50–150 nm membrane-bound vesicles [30] encapsulate cytoplasmic contents such as RNA and protein during formation and are subsequently released into the extracellular space.…”

Section: Introductionmentioning

confidence: 99%

Exosomes are released by bystander cells exposed to radiation-induced biophoton signals: Reconciling the mechanisms mediating the bystander effect

Fernández-Palomo

McNeill

et al. 2017

PLoS ONE

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ObjectiveThe objective of our study was to explore a possible molecular mechanism by which ultraviolet (UV) biophotons could elicit bystander responses in reporter cells and resolve the problem of seemingly mutually exclusive mechanisms of a physical UV signal & a soluble factor-mediated bystander signal.MethodsThe human colon carcinoma cell line, HCT116 p53 +/+, was directly irradiated with 0.5 Gy tritium beta particles to induce ultraviolet biophoton emission. Bystander cells were not directly irradiated but were exposed to the emitted UV biophotons. Medium was subsequently harvested from UV-exposed bystander cells. The exosomes extracted from this medium were incubated with reporter cell populations. These reporter cells were then assayed for clonogenic survival and mitochondrial membrane potential with and without prior treatment of the exosomes with RNase.ResultsClonogenic cell survival was significantly reduced in reporter cells incubated with exosomes extracted from cells exposed to secondarily-emitted UV. These exosomes also induced significant mitochondrial membrane depolarization in receiving reporter cells. Conversely, exosomes extracted from non-UV-exposed cells did not produce bystander effects in reporter cells. The treatment of exosomes with RNase prior to their incubation with reporter cells effectively abolished bystander effects in reporter cells and this suggests a role for RNA in mediating the bystander response elicited by UV biophotons and their produced exosomes.ConclusionThis study supports a role for exosomes released from UV biophoton-exposed bystander cells in eliciting bystander responses and also indicates a reconciliation between the UV-mediated bystander effect and the bystander effect which has been suggested in the literature to be mediated by soluble factors.

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The non-targeted effects of radiation are perpetuated by exosomes

Cited by 142 publications

References 48 publications

Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells

Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells

Radiotherapy for Non–Small Cell Lung Cancer Induces DNA Damage Response in Both Irradiated and Out-of-field Normal Tissues

Exosomes are released by bystander cells exposed to radiation-induced biophoton signals: Reconciling the mechanisms mediating the bystander effect

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