Your browser doesn't support javascript.
loading
Energy Metabolism, Metabolite, and Inflammatory Profiles in Human Ex Vivo Adipose Tissue Are Influenced by Obesity Status, Metabolic Dysfunction, and Treatment Regimes in Patients with Oesophageal Adenocarcinoma.
O'Connell, Fiona; Mylod, Eimear; Donlon, Noel E; Heeran, Aisling B; Butler, Christine; Bhardwaj, Anshul; Ramjit, Sinead; Durand, Michael; Lambe, Gerard; Tansey, Paul; Welartne, Ivan; Sheahan, Kevin P; Yin, Xiaofei; Donohoe, Claire L; Ravi, Narayanasamy; Dunne, Margaret R; Brennan, Lorraine; Reynolds, John V; Roche, Helen M; O'Sullivan, Jacintha.
Afiliación
  • O'Connell F; Department of Surgery, Trinity St. James's Cancer Institute and Trinity Translational Medicine Institute, St. James's Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland.
  • Mylod E; Department of Surgery, Trinity St. James's Cancer Institute and Trinity Translational Medicine Institute, St. James's Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland.
  • Donlon NE; Cancer Immunology and Immunotherapy Group, Department of Surgery, Trinity College Dublin, St. James's Hospital, D08 W9RT Dublin, Ireland.
  • Heeran AB; Department of Surgery, Trinity St. James's Cancer Institute and Trinity Translational Medicine Institute, St. James's Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland.
  • Butler C; Cancer Immunology and Immunotherapy Group, Department of Surgery, Trinity College Dublin, St. James's Hospital, D08 W9RT Dublin, Ireland.
  • Bhardwaj A; Department of Surgery, Trinity St. James's Cancer Institute and Trinity Translational Medicine Institute, St. James's Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland.
  • Ramjit S; Department of Surgery, Trinity St. James's Cancer Institute and Trinity Translational Medicine Institute, St. James's Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland.
  • Durand M; Department of Surgery, Trinity St. James's Cancer Institute and Trinity Translational Medicine Institute, St. James's Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland.
  • Lambe G; Department of Surgery, Trinity St. James's Cancer Institute and Trinity Translational Medicine Institute, St. James's Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland.
  • Tansey P; Department of Radiology, St. James's Hospital, D08 NHY1 Dublin, Ireland.
  • Welartne I; Department of Radiology, St. James's Hospital, D08 NHY1 Dublin, Ireland.
  • Sheahan KP; Department of Radiology, St. James's Hospital, D08 NHY1 Dublin, Ireland.
  • Yin X; Department of Radiology, St. James's Hospital, D08 NHY1 Dublin, Ireland.
  • Donohoe CL; Department of Radiology, Beaumont Hospital, D02 YN77 Dublin, Ireland.
  • Ravi N; UCD School of Agriculture and Food Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland.
  • Dunne MR; Department of Surgery, Trinity St. James's Cancer Institute and Trinity Translational Medicine Institute, St. James's Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland.
  • Brennan L; Department of Surgery, Trinity St. James's Cancer Institute and Trinity Translational Medicine Institute, St. James's Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland.
  • Reynolds JV; Department of Surgery, Trinity St. James's Cancer Institute and Trinity Translational Medicine Institute, St. James's Hospital and Trinity College Dublin, D08 W9RT Dublin, Ireland.
  • Roche HM; School of Chemical & Biopharmaceutical Sciences, Technological University Dublin, Tallaght, D07 EWV4 Dublin, Ireland.
  • O'Sullivan J; UCD School of Agriculture and Food Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland.
Cancers (Basel) ; 15(6)2023 Mar 09.
Article en En | MEDLINE | ID: mdl-36980567
ABSTRACT
Oesophageal adenocarcinoma (OAC) is a poor prognosis cancer with limited response rates to current treatment modalities and has a strong link to obesity. To better elucidate the role of visceral adiposity in this disease state, a full metabolic profile combined with analysis of secreted pro-inflammatory cytokines, metabolites, and lipid profiles were assessed in human ex vivo adipose tissue explants from obese and non-obese OAC patients. These data were then related to extensive clinical data including obesity status, metabolic dysfunction, previous treatment exposure, and tumour regression grades. Real-time energy metabolism profiles were assessed using the seahorse technology. Adipose explant conditioned media was screened using multiplex ELISA to assess secreted levels of 54 pro-inflammatory mediators. Targeted secreted metabolite and lipid profiles were analysed using Ultra-High-Performance Liquid Chromatography coupled with Mass Spectrometry. Adipose tissue explants and matched clinical data were collected from OAC patients (n = 32). Compared to visceral fat from non-obese patients (n = 16), visceral fat explants from obese OAC patients (n = 16) had significantly elevated oxidative phosphorylation metabolism profiles and an increase in Eotaxin-3, IL-17A, IL-17D, IL-3, MCP-1, and MDC and altered secretions of glutamine associated metabolites. Adipose explants from patients with metabolic dysfunction correlated with increased oxidative phosphorylation metabolism, and increases in IL-5, IL-7, SAA, VEGF-C, triacylglycerides, and metabolites compared with metabolically healthy patients. Adipose explants generated from patients who had previously received neo-adjuvant chemotherapy (n = 14) showed elevated secretions of pro-inflammatory mediators, IL-12p40, IL-1α, IL-22, and TNF-ß and a decreased expression of triacylglycerides. Furthermore, decreased secreted levels of triacylglycerides were also observed in the adipose secretome of patients who received the chemotherapy-only regimen FLOT compared with patients who received no neo-adjuvant treatment or chemo-radiotherapy regimen CROSS. For those patients who showed the poorest response to currently available treatments, their adipose tissue was associated with higher glycolytic metabolism compared to patients who had good treatment responses. This study demonstrates that the adipose secretome in OAC patients is enriched with mediators that could prime the tumour microenvironment to aid tumour progression and attenuate responses to conventional cancer treatments, an effect which appears to be augmented by obesity and metabolic dysfunction and exposure to different treatment regimes.
Palabras clave

Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: Cancers (Basel) Año: 2023 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: Cancers (Basel) Año: 2023 Tipo del documento: Article