Journal article
Cancer-associated fibroblasts predict poor outcome and promote periostin-dependent invasion in oesophageal adenocarcinoma
TJ Underwood, AL Hayden, M Derouet, E Garcia, F Noble, MJ White, S Thirdborough, A Mead, N Clemons, M Mellone, C Uzoho, JN Primrose, JP Blaydes, GJ Thomas
Journal of Pathology | Published : 2015
DOI: 10.1002/path.4467
Abstract
Interactions between cancer cells and cancer-associated fibroblasts (CAFs) play an important role in tumour development and progression. In this study we investigated the functional role of CAFs in oesophageal adenocarcinoma (EAC). We used immunochemistry to analyse a cohort of 183 EAC patients for CAF markers related to disease mortality. We characterized CAFs and normal oesophageal fibroblasts (NOFs) using western blotting, immunofluorescence and gel contraction. Transwell assays, 3D organotypic culture and xenograft models were used to examine the effects on EAC cell function and to dissect molecular mechanisms regulating invasion. Most EACs (93%) contained CAFs with a myofibroblastic (α-..
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Awarded by Medical Research Council
Funding Acknowledgements
The work presented here is supported by a UK Medical Research Council Clinician Scientist award to TJU. The authors thank Dr Patrick Duriez (CRUK Protein Core Facility, University of Southampton) for the production of recombinant periostin; Mr Jamie Kelly, Mr James Byrne, Mr Ian Bailey, Sister Donna Sharland and Nina Hollings (Oesophagogastric Cancer Centre, University Hospital Southampton); the University of Southampton Experimental Cancer Medicine Centre Tumour Bank (ECMC), particularly Lisa Boulter and Kathy Potter; and the patients involved in this study.