Visceral Adipose Tissue Modulates Radiosensitivity in Oesophageal Adenocarcinoma

Int J Med Sci. 2019 Apr 5;16(4):519-528. doi: 10.7150/ijms.29296. eCollection 2019.


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 vivo study 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.

Keywords: obesity; oesophageal cancer; radiotherapy; visceral adipose tissue.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma / radiotherapy*
  • Body Mass Index
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Culture Media, Conditioned / pharmacology
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / radiotherapy*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Humans
  • Intra-Abdominal Fat / drug effects*
  • Intra-Abdominal Fat / pathology
  • Male
  • Metabolomics
  • Obesity, Abdominal / genetics
  • Obesity, Abdominal / pathology
  • Obesity, Abdominal / radiotherapy*
  • Radiation Tolerance / drug effects*
  • Receptors, Adiponectin / genetics
  • Receptors, Leptin / radiation effects


  • ADIPOR1 protein, human
  • ADIPOR2 protein, human
  • Culture Media, Conditioned
  • Receptors, Adiponectin
  • Receptors, Leptin

Supplementary concepts

  • Adenocarcinoma Of Esophagus