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Quantitative proteomic profiling of primary cancer-associated fibroblasts in oesophageal adenocarcinoma.
Manousopoulou, Antigoni; Hayden, Annette; Mellone, Massimiliano; Garay-Baquero, Diana J; White, Cory H; Noble, Fergus; Lopez, Monette; Thomas, Gareth J; Underwood, Timothy J; Garbis, Spiros D.
Afiliación
  • Manousopoulou A; Institute for Life Sciences, University of Southampton, Southampton, UK.
  • Hayden A; Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Mellone M; Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Garay-Baquero DJ; Clinical and Experimental Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
  • White CH; Clinical and Experimental Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Noble F; Merck Exploratory Science Center, Cambridge, MA, USA.
  • Lopez M; Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Thomas GJ; University Hospital Southampton NHS Foundation Trust, Southampton, UK.
  • Underwood TJ; Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Garbis SD; Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK. T.J.Underwood@soton.ac.uk.
Br J Cancer ; 118(9): 1200-1207, 2018 05.
Article en En | MEDLINE | ID: mdl-29593339
BACKGROUND: Cancer-associated fibroblasts (CAFs) form the major stromal component of the tumour microenvironment (TME). The present study aimed to examine the proteomic profiles of CAFs vs. normal fibroblasts (NOFs) from patients with oesophageal adenocarcinoma to gain insight into their pro-oncogenic phenotype. METHODS: CAFs/NOFs from four patients were sub-cultured and analysed using quantitative proteomics. Differentially expressed proteins (DEPs) were subjected to bioinformatics and compared with published proteomics and transcriptomics  datasets. RESULTS: Principal component analysis of all profiled proteins showed that CAFs had high heterogeneity and clustered separately from NOFs. Bioinformatics interrogation of the DEPs demonstrated inhibition of adhesion of epithelial cells, adhesion of connective tissue cells and cell death of fibroblast cell lines in CAFs vs. NOFs (p < 0.0001). KEGG pathway analysis showed a significant enrichment of the insulin-signalling pathway (p = 0.03). Gene ontology terms related with myofibroblast phenotype, metabolism, cell adhesion/migration, hypoxia/oxidative stress, angiogenesis, immune/inflammatory response were enriched in CAFs vs. NOFs. Nestin, a stem-cell marker up-regulated in CAFs vs. NOFs, was confirmed to be expressed in the TME with immunohistochemistry. CONCLUSIONS: The identified pathways and participating proteins may provide novel insight on the tumour-promoting properties of CAFs and unravel novel adjuvant therapeutic targets in the TME.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Esofágicas / Adenocarcinoma / Proteoma / Fibroblastos / Fibroblastos Asociados al Cáncer Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Br J Cancer Año: 2018 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Esofágicas / Adenocarcinoma / Proteoma / Fibroblastos / Fibroblastos Asociados al Cáncer Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Br J Cancer Año: 2018 Tipo del documento: Article Pais de publicación: Reino Unido