Cancer-associated fibroblasts predict poor outcome and promote periostin-dependent invasion in oesophageal adenocarcinoma
| Autor: | Timothy J. Underwood, Nicholas J. Clemons, S Thirdborough, Fergus Noble, Gareth J. Thomas, Massimiliano Mellone, Annette Hayden, Mathieu Derouet, Michael J. White, Edwin Garcia, Abbie Mead, Jeremy P. Blaydes, Chudy Uzoho, John N. Primrose |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty oesophageal cancer Stromal cell Esophageal Neoplasms Mice SCID Periostin Biology Adenocarcinoma In Vitro Techniques Pathology and Forensic Medicine Cohort Studies Mice Phosphatidylinositol 3-Kinases Esophagus Cell Movement medicine Biomarkers Tumor Tumor Microenvironment Animals Humans Cells Cultured Aged periostin Aged 80 and over Tumor microenvironment CAFs Matricellular protein Fibroblasts Middle Aged medicine.disease Prognosis Original Papers Actins Desmoplasia Survival Rate Disease Models Animal Cancer cell Cancer-Associated Fibroblasts Heterografts Female medicine.symptom tumour microenvironment Cell Adhesion Molecules Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | The Journal of Pathology |
| ISSN: | 1096-9896 0022-3417 |
| Popis: | Interactions between cancer cells and cancer-associated fibroblasts (CAF) play an important role in tumour development and progression. In this study we investigated the functional role of CAF in oesophageal adenocarcinoma (EAC). We used immunochemistry to analyse a cohort of EAC patients (183 patients) for CAF markers related to disease mortality. We characterized CAF and normal oesophageal fibroblasts (NOF) using western blotting, immunofluorescence and gel contraction. Transwell assays, 3-D organotypic culture and xenograft models were used to examine effects on EAC cell function, and dissect molecular mechanisms regulating invasion. Most EAC (93%) contained CAF with a myofibroblastic (?-SMA-positive) phenotype, which correlated significantly with poor survival (p?=?0.016; HR 7. 1 (1.7-29.4). Primary CAF, isolated from EAC, have a contractile, myofibroblastic phenotype, and promote EAC cell invasion in vitro (Transwell assays, p?=? |
| Databáze: | OpenAIRE |
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