Type

Journal Article

Authors

Jacintha OʼSullivan
John V Reynolds
Lorraine Brennan
Melissa J Conroy
Aoife Cannon
Eibhlin Carr
Joanne Lysaght
Rory Casey
Suzanne Doyle
Graham Pidgeon
and 2 others

Subjects

Biochemistry

Topics
radiotherapy visceral adipose tissue medicine and health sciences magnetic resonance spectroscopy nuclear magnetic resonance biology cell and developmental biology gene expression profiling oesophageal adenocarcinoma oesophageal cancer obesity

Visceral Adipose Tissue Modulates Radiosensitivity in Oesophageal Adenocarcinoma. (2019)

Abstract Oesophageal adenocarcinoma (OAC) is an exemplar model of obesity-associated cancer. Response to neoadjuvant chemoradiotherapy (NA CRT) is a clinical challenge. We examined if visceral adipose tissue and obesity status alter radiosensitivity in OAC.The radioresistant (OE33R) and radioresponsive (OE33P) OAC isogenic model was cultured with adipose tissue conditioned media from three patient cohorts: non-cancer patients, surgery only OAC patients and NA CRT OAC patients. Cell survival was characterised by clonogenic assay, metabolomic profiling by nuclear magnetic resonance spectroscopy and adipokine receptor gene expression by qPCR. A retrospective in vivostudy compared tumour response to NA CRT in normal weight (n=53) versus overweight/obese patients (n=148). Adipose conditioned media (ACM) from all patient cohorts significantly increased radiosensitivity in radioresistant OE33R cells. ACM from the NA CRT OAC cohort increased radiosensitivity in OE33P cells. Metabolomic profiling demonstrated separation of the non-cancer and surgery only OAC cohorts and between the non-cancer and NA CRT OAC cohorts. Gene expression profiling of OE33P versus OE33R cells demonstrated differential expression of the adiponectin receptor-1 (AR1), adiponectin receptor-2 (AR2), leptin receptor (LepR) and neuropilin receptor-1 (NRP1) genes. In vivo overweight/obese OAC patients achieved an enhanced tumour response following NA CRT compared to normal weight patients. This study demonstrates that visceral adipose tissue modulates the cellular response to radiation in OAC.
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Full list of authors on original publication

Jacintha OʼSullivan, John V Reynolds, Lorraine Brennan, Melissa J Conroy, Aoife Cannon, Eibhlin Carr, Joanne Lysaght, Rory Casey, Suzanne Doyle, Graham Pidgeon and 2 others

Experts in our system

1
J V Reynolds
Trinity College Dublin
Total Publications: 206
 
2
Lorraine Brennan
University College Dublin
Total Publications: 166
 
3
Melissa J Conroy
Trinity College Dublin
Total Publications: 14
 
4
Aoife Cannon
TU Dublin
 
5
Eibhlin Carr
Trinity College Dublin
Total Publications: 3
 
6
Joanne Lysaght
Trinity College Dublin
Total Publications: 39
 
7
Rory Casey
Trinity College Dublin
Total Publications: 4
 
8
Suzanne L Doyle
Trinity College Dublin
Total Publications: 23
 
9
Graham Pidgeon
Trinity College Dublin
Total Publications: 38