OC-121 Fibroblast activation in the tumour microenvironment promotes tumour cell invasion and resistance to chemotherapy in oesophageal adenocarcinoma

IntroductionStromal and other non-malignant cells have the potential to undergo modifications that can synergistically create a supportive microenvironment for tumour growth, invasion and metastasis. Oesophageal adenocarcinoma (EAC) is characterised by early invasion, leading to metastatic disease and therefore only 20% of patients are suitable for treatment with curative intent. Cancer associated fibroblasts (CAFs) have an activated, myofibroblastic phenotype and have been recognised as mediators of tumour progression in a range of solid tumours. This study investigates the role of CAFs in EAC invasion and resistance to chemotherapy.MethodsFunctional biological analyses comparing primary fibroblasts from tumour stroma (CAF) and normal oesophagus (NOF) were carried out using organotypic culture, transwell invasion assays, collagen-1 gel contraction assays, siRNA gene silencing and colony forming assays. T-Tests (>95% CI) were carried out for all statistical analyses.ResultsPrimary oesophageal CAFs displayed an activated phenotype as demonstrated by α-SMA expression and increased collagen-1 gel contraction in comparison to NOFs (p