Radiation-induced Bystander Effect (RIBE) alters mitochondrial metabolism using a human rectal cancer ex vivo explant model

Aisling B Heeran; Helen P Berrigan; Croí E Buckley; Heleena Moni Bottu; Orla Prendiville; Amy M Buckley; Niamh Clarke; Noel E Donlon; Timothy S Nugent; Michael Durand; Cara Dunne; John O Larkin; Brian Mehigan; Paul McCormick; Lorraine Brennan; Niamh Lynam-Lennon; Jacintha O'Sullivan

doi:10.1016/j.tranon.2020.100882

Radiation-induced Bystander Effect (RIBE) alters mitochondrial metabolism using a human rectal cancer ex vivo explant model

Aisling B Heeran
, Helen P Berrigan
, Croí E Buckley
, Heleena Moni Bottu
, Orla Prendiville
, Amy M Buckley
, Niamh Clarke
, Noel E Donlon
, Timothy S Nugent
, Michael Durand
, Cara Dunne
, John O Larkin
, Brian Mehigan
, Paul McCormick
, Lorraine Brennan
, Niamh Lynam-Lennon
, Jacintha O'Sullivan

Pharmacy

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

Abstract

Locally advanced rectal cancer is treated with neoadjuvant-chemoradiotherapy, however only 22% of patients achieve a complete response. Resistance mechanisms are poorly understood. Radiation-induced Bystander Effect (RIBE) describes the effect of radiation on neighbouring unirradiated cells. We investigated the effects of ex vivo RIBEinduction from normal and rectal cancer tissue on bystander cell metabolism, mitochondrial function and metabolomic profiling. We correlated bystander events to patient clinical characteristics. Ex vivo RIBE-induction caused metabolic alterations in bystander cells, specifically reductions in OXPHOS following RIBE-induction in normal (p = 0.01) and cancer tissue (p = 0.03) and reduced glycolysis following RIBE-induction in cancer tissue (p = 0.01). Visceral fat area correlated with glycolysis (p = 0.02) and ATP production (p = 0.03) following exposure of cells to TCM from irradiated cancer biopsies. Leucine levels were reduced in the irradiated cancer compared to the irradiated normal secretome (p = 0.04). ROS levels were higher in cells exposed to the cancer compared to the normal secretome (p = 0.04).

RIBE-induction ex vivo causes alterations in the metabolome in normal and malignant rectal tissue along with metabolic alterations in bystander cellular metabolism. This may offer greater understanding of the effects of RIBE on metabolism, mitochondrial function and the secreted metabolome.

Original language	English
Article number	100882
Pages (from-to)	1-10
Journal	Translational Oncology
Volume	14
Early online date	31 Dec 2021
DOIs	https://doi.org/10.1016/j.tranon.2020.100882
Publication status	Published - 31 Dec 2021

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SDG 3 Good Health and Well-being

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10.1016/j.tranon.2020.100882

https://hdl.handle.net/1959.11/61211

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Heeran, A. B., Berrigan, H. P., Buckley, C. E., Bottu, H. M., Prendiville, O., Buckley, A. M., Clarke, N., Donlon, N. E., Nugent, T. S., Durand, M., Dunne, C., Larkin, J. O., Mehigan, B., McCormick, P., Brennan, L., Lynam-Lennon, N., & O'Sullivan, J. (2021). Radiation-induced Bystander Effect (RIBE) alters mitochondrial metabolism using a human rectal cancer ex vivo explant model. Translational Oncology, 14, 1-10. Article 100882. https://doi.org/10.1016/j.tranon.2020.100882

@article{b9640e8155aa43e780812877e2b13bd2,

title = "Radiation-induced Bystander Effect (RIBE) alters mitochondrial metabolism using a human rectal cancer ex vivo explant model",

abstract = "Locally advanced rectal cancer is treated with neoadjuvant-chemoradiotherapy, however only 22\% of patients achieve a complete response. Resistance mechanisms are poorly understood. Radiation-induced Bystander Effect (RIBE) describes the effect of radiation on neighbouring unirradiated cells. We investigated the effects of ex vivo RIBEinduction from normal and rectal cancer tissue on bystander cell metabolism, mitochondrial function and metabolomic profiling. We correlated bystander events to patient clinical characteristics. Ex vivo RIBE-induction caused metabolic alterations in bystander cells, specifically reductions in OXPHOS following RIBE-induction in normal (p = 0.01) and cancer tissue (p = 0.03) and reduced glycolysis following RIBE-induction in cancer tissue (p = 0.01). Visceral fat area correlated with glycolysis (p = 0.02) and ATP production (p = 0.03) following exposure of cells to TCM from irradiated cancer biopsies. Leucine levels were reduced in the irradiated cancer compared to the irradiated normal secretome (p = 0.04). ROS levels were higher in cells exposed to the cancer compared to the normal secretome (p = 0.04). RIBE-induction ex vivo causes alterations in the metabolome in normal and malignant rectal tissue along with metabolic alterations in bystander cellular metabolism. This may offer greater understanding of the effects of RIBE on metabolism, mitochondrial function and the secreted metabolome.",

author = "Heeran, \{Aisling B\} and Berrigan, \{Helen P\} and Buckley, \{Cro{\'i} E\} and Bottu, \{Heleena Moni\} and Orla Prendiville and Buckley, \{Amy M\} and Niamh Clarke and Donlon, \{Noel E\} and Nugent, \{Timothy S\} and Michael Durand and Cara Dunne and Larkin, \{John O\} and Brian Mehigan and Paul McCormick and Lorraine Brennan and Niamh Lynam-Lennon and Jacintha O'Sullivan",

year = "2021",

month = dec,

day = "31",

doi = "10.1016/j.tranon.2020.100882",

language = "English",

volume = "14",

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journal = "Translational Oncology",

issn = "1944-7124",

publisher = "Neoplasia Press",

}

Heeran, AB, Berrigan, HP, Buckley, CE, Bottu, HM, Prendiville, O, Buckley, AM, Clarke, N, Donlon, NE, Nugent, TS, Durand, M, Dunne, C, Larkin, JO, Mehigan, B, McCormick, P, Brennan, L, Lynam-Lennon, N & O'Sullivan, J 2021, 'Radiation-induced Bystander Effect (RIBE) alters mitochondrial metabolism using a human rectal cancer ex vivo explant model', Translational Oncology, vol. 14, 100882, pp. 1-10. https://doi.org/10.1016/j.tranon.2020.100882

TY - JOUR

T1 - Radiation-induced Bystander Effect (RIBE) alters mitochondrial metabolism using a human rectal cancer ex vivo explant model

AU - Heeran, Aisling B

AU - Berrigan, Helen P

AU - Buckley, Croí E

AU - Bottu, Heleena Moni

AU - Prendiville, Orla

AU - Buckley, Amy M

AU - Clarke, Niamh

AU - Donlon, Noel E

AU - Nugent, Timothy S

AU - Durand, Michael

AU - Dunne, Cara

AU - Larkin, John O

AU - Mehigan, Brian

AU - McCormick, Paul

AU - Brennan, Lorraine

AU - Lynam-Lennon, Niamh

AU - O'Sullivan, Jacintha

PY - 2021/12/31

Y1 - 2021/12/31

N2 - Locally advanced rectal cancer is treated with neoadjuvant-chemoradiotherapy, however only 22% of patients achieve a complete response. Resistance mechanisms are poorly understood. Radiation-induced Bystander Effect (RIBE) describes the effect of radiation on neighbouring unirradiated cells. We investigated the effects of ex vivo RIBEinduction from normal and rectal cancer tissue on bystander cell metabolism, mitochondrial function and metabolomic profiling. We correlated bystander events to patient clinical characteristics. Ex vivo RIBE-induction caused metabolic alterations in bystander cells, specifically reductions in OXPHOS following RIBE-induction in normal (p = 0.01) and cancer tissue (p = 0.03) and reduced glycolysis following RIBE-induction in cancer tissue (p = 0.01). Visceral fat area correlated with glycolysis (p = 0.02) and ATP production (p = 0.03) following exposure of cells to TCM from irradiated cancer biopsies. Leucine levels were reduced in the irradiated cancer compared to the irradiated normal secretome (p = 0.04). ROS levels were higher in cells exposed to the cancer compared to the normal secretome (p = 0.04). RIBE-induction ex vivo causes alterations in the metabolome in normal and malignant rectal tissue along with metabolic alterations in bystander cellular metabolism. This may offer greater understanding of the effects of RIBE on metabolism, mitochondrial function and the secreted metabolome.

AB - Locally advanced rectal cancer is treated with neoadjuvant-chemoradiotherapy, however only 22% of patients achieve a complete response. Resistance mechanisms are poorly understood. Radiation-induced Bystander Effect (RIBE) describes the effect of radiation on neighbouring unirradiated cells. We investigated the effects of ex vivo RIBEinduction from normal and rectal cancer tissue on bystander cell metabolism, mitochondrial function and metabolomic profiling. We correlated bystander events to patient clinical characteristics. Ex vivo RIBE-induction caused metabolic alterations in bystander cells, specifically reductions in OXPHOS following RIBE-induction in normal (p = 0.01) and cancer tissue (p = 0.03) and reduced glycolysis following RIBE-induction in cancer tissue (p = 0.01). Visceral fat area correlated with glycolysis (p = 0.02) and ATP production (p = 0.03) following exposure of cells to TCM from irradiated cancer biopsies. Leucine levels were reduced in the irradiated cancer compared to the irradiated normal secretome (p = 0.04). ROS levels were higher in cells exposed to the cancer compared to the normal secretome (p = 0.04). RIBE-induction ex vivo causes alterations in the metabolome in normal and malignant rectal tissue along with metabolic alterations in bystander cellular metabolism. This may offer greater understanding of the effects of RIBE on metabolism, mitochondrial function and the secreted metabolome.

U2 - 10.1016/j.tranon.2020.100882

DO - 10.1016/j.tranon.2020.100882

M3 - Article

SN - 1944-7124

VL - 14

SP - 1

EP - 10

JO - Translational Oncology

JF - Translational Oncology

M1 - 100882

ER -

Radiation-induced Bystander Effect (RIBE) alters mitochondrial metabolism using a human rectal cancer ex vivo explant model

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