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

Autor:	Heeran AB; Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Dublin 8, Ireland., Berrigan HP; Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Dublin 8, Ireland., Buckley CE; Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Dublin 8, Ireland., Bottu HM; Institute of Food and Health and Conway Institute, UCD School of Agriculture and Food Science, UCD, Belfield, Dublin 4, Ireland., Prendiville O; Institute of Food and Health and Conway Institute, UCD School of Agriculture and Food Science, UCD, Belfield, Dublin 4, Ireland., Buckley AM; Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Dublin 8, Ireland., Clarke N; Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Dublin 8, Ireland., Donlon NE; Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Dublin 8, Ireland., Nugent TS; Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Dublin 8, Ireland., Durand M; GEMS, St. James's Hospital, Dublin 8, Ireland., Dunne C; GEMS, St. James's Hospital, Dublin 8, Ireland., Larkin JO; GEMS, St. James's Hospital, Dublin 8, Ireland., Mehigan B; GEMS, St. James's Hospital, Dublin 8, Ireland., McCormick P; GEMS, St. James's Hospital, Dublin 8, Ireland., Brennan L; Institute of Food and Health and Conway Institute, UCD School of Agriculture and Food Science, UCD, Belfield, Dublin 4, Ireland., Lynam-Lennon N; Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Dublin 8, Ireland., O'Sullivan J; Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Dublin 8, Ireland. Electronic address: osullij4@tcd.ie.
Jazyk:	angličtina
Zdroj:	Translational oncology [Transl Oncol] 2021 Jan; Vol. 14 (1), pp. 100882. Date of Electronic Publication: 2020 Oct 23.
DOI:	10.1016/j.tranon.2020.100882
Abstrakt:	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 RIBE-induction 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. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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