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Quantitative proteomic profiling of primary cancer-associated fibroblasts in oesophageal adenocarcinoma: CAF proteomic profiling in OAC

Quantitative proteomic profiling of primary cancer-associated fibroblasts in oesophageal adenocarcinoma: CAF proteomic profiling in OAC
Quantitative proteomic profiling of primary cancer-associated fibroblasts in oesophageal adenocarcinoma: CAF proteomic profiling in OAC
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.
0007-0920
1200-1207
Manousopoulou, Antigoni
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Hayden, Annette
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Mellone, Massimiliano
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Garay Baquero, Diana J.
856045e8-eed9-4bbf-9b1c-5985a19d7af3
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
9a5e4e75-cea9-4d0b-91c8-0fa2af02632f
Hayden, Annette
80301564-d83f-404c-abd0-0f8acf6c2e60
Mellone, Massimiliano
b0301b32-14f8-4203-9026-b7f90885cab9
Garay Baquero, Diana J.
856045e8-eed9-4bbf-9b1c-5985a19d7af3
White, Cory H.
45233a78-f0c9-4696-8aaf-1b2673f83c91
Noble, Fergus
4f14574c-28f2-4e04-bd95-f53c7649e1fa
Lopez, Monette
ddb501fb-a414-4b3f-87df-439b0b4c89d4
Thomas, Gareth J.
2ff54aa9-a766-416b-91ee-cf1c5be74106
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: CAF proteomic profiling in OAC. British Journal of Cancer, 118 (9), 1200-1207. (doi:10.1038/s41416-018-0042-9).

Record type: Article

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.

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Manousopoulou et al_CAF proteomic profiling in OAC_MD-2017-3414R1 - Accepted Manuscript
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More information

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: https://eprints.soton.ac.uk/id/eprint/417703
ISSN: 0007-0920
PURE UUID: f69d9b12-43b1-4ffa-8aa0-f70f9d9311a6
ORCID for Massimiliano Mellone: ORCID iD orcid.org/0000-0002-4964-9340
ORCID for Diana J. Garay Baquero: ORCID iD orcid.org/0000-0002-9450-8504
ORCID for Timothy J. Underwood: ORCID iD orcid.org/0000-0001-9455-2188

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Date deposited: 12 Feb 2018 17:30
Last modified: 14 Mar 2019 05:16

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