Quantitative proteomic profiling of primary cancer-associated fibroblasts in oesophageal adenocarcinoma
Quantitative proteomic profiling of primary cancer-associated fibroblasts in oesophageal adenocarcinoma
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 usingquantitative 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.
1200-1207
Manousopoulou, Antigoni
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Hayden, Annette
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Mellone, Massimiliano
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Garay-Baquero, Diana J.
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White, Cory H.
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Noble, Fergus
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Lopez, Monette
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Thomas, Gareth J.
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Underwood, Timothy J.
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Garbis, Spiros D.
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29 March 2018
Manousopoulou, Antigoni
4e4b92ba-be65-4dba-a15d-87924c56f08b
Hayden, Annette
3a43aee1-3ff0-4182-956d-b6c7b3a7f8be
Mellone, Massimiliano
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Garay-Baquero, Diana J.
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White, Cory H.
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Noble, Fergus
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Lopez, Monette
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Thomas, Gareth J.
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Underwood, Timothy J.
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Garbis, Spiros D.
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Manousopoulou, Antigoni, Hayden, Annette, Mellone, Massimiliano, Garay-Baquero, Diana J., White, Cory H., Noble, Fergus, Lopez, Monette, Thomas, Gareth J., Underwood, Timothy J. and Garbis, Spiros D.
(2018)
Quantitative proteomic profiling of primary cancer-associated fibroblasts in oesophageal adenocarcinoma.
British Journal of Cancer, 118 (9), .
(doi:10.1038/s41416-018-0042-9).
Abstract
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 usingquantitative 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.
Text
Manousopoulou et al_CAF proteomic profiling in OAC_MD-2017-3414R1
- Accepted Manuscript
Text
s41416-018-0042-9
- Version of Record
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Accepted/In Press date: 30 January 2018
e-pub ahead of print date: 29 March 2018
Published date: 29 March 2018
Identifiers
Local EPrints ID: 417703
URI: http://eprints.soton.ac.uk/id/eprint/417703
ISSN: 0007-0920
PURE UUID: f69d9b12-43b1-4ffa-8aa0-f70f9d9311a6
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Date deposited: 12 Feb 2018 17:30
Last modified: 11 Jul 2024 04:06
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Contributors
Author:
Antigoni Manousopoulou
Author:
Annette Hayden
Author:
Massimiliano Mellone
Author:
Diana J. Garay-Baquero
Author:
Cory H. White
Author:
Fergus Noble
Author:
Monette Lopez
Author:
Spiros D. Garbis
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