ABSTRACT
Background: Barrett's oesophagus (BO) is a pre-malignant condition in which normal squamous epithelium of the lower oesophagus and gastresophageal junction is replaced by columnar cells and progress to oesophageal adenocarcinoma. The increase burden of oesophagus cancer morbidity and mortality worldwide make study of factors involved in the pathogenesis of BO essential. However, most of studies that examine the environmental risk factors associated with increased incidence and prevalence of BO have largely ignored the potential role of bacteria in disease aetiology. Aims: This study examined the role of Campylobacter concisus isolated from Barrett's and adenocarcinoma patient samples as one of possible environmental factors in the progression of Barrett's oesophagus to oesophagus adenocarcinoma. Methods: We focused on the effect of C. concisus on the expression caudal type homeobox 1 gene (CDX1) and cyclooxygenase-2 (COX-2) in three BO cell lines using quantitative real-time PCR. In addition, the attachment and invasion characteristics of C. concisus were also tested. Results: Results showed that C. concisus had a strong attachment to the cell lines and induce the expression of CDX1 in Barrett's cell lines in a time-dependent manner. Conclusion: Findings indicate that C. concisus could be as a new challenge in the progression of BO to adenocarcinoma.
Subject(s)
Barrett Esophagus/metabolism , Campylobacter Infections/complications , Campylobacter/pathogenicity , Cyclooxygenase 2/metabolism , Esophageal Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Homeodomain Proteins/metabolism , Adenocarcinoma/etiology , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Barrett Esophagus/etiology , Barrett Esophagus/pathology , Biomarkers, Tumor/metabolism , Campylobacter Infections/microbiology , Esophageal Neoplasms/etiology , Esophageal Neoplasms/pathology , Esophagus/metabolism , Esophagus/microbiology , Esophagus/pathology , Humans , Tumor Cells, CulturedABSTRACT
Barrett's oesophagus (BO) is a complicated condition at the gastroesophageal junction in which normal squamous epithelium is changed to columnar and leads to oesophageal adenocarcinoma (OA). In the past decades, the prevalence of Barrett's disease and mortality rate of adenocarcinoma has significantly increased throughout the word. Data has shown that molecular pathogenesis of disease has not been clearly identified. However, a wide-range and successful administration of probiotics in cancer and gastrointestinal diseases has lead to the investigation into the possible inhibitory role of probiotics in oesophageal cancer. This study was conducted to evaluate the inhibitory effect of probiotics on the expression of biomarkers in an in vitro model. Two different Barrett's oesophageal cell lines were selected to co-culture with B. longum and Lactobacillus acidophilus to measure expression of IL-18, TNFα, p53 (tumour suppressor gene), cyclooxygenase 2 and CDX1 (caudal type homeobox 1) genes. In addition, two different aspects of probiotic administration, therapeutic and prophylactic test were also examined. Results showed that micro-organisms could inhibit expression of biomarkers and therapeutic culture conditions were more effective than prophylactic tests. The results obtained suggest that it is possible to incorporate the administration of probiotics in BO and OA prevention.
Subject(s)
Barrett Esophagus/pathology , Bifidobacterium/growth & development , Biomarkers/analysis , Lactobacillus acidophilus/growth & development , Probiotics/pharmacology , Barrett Esophagus/prevention & control , Barrett Esophagus/therapy , Cell Line, Tumor , Gene Expression Profiling , Humans , Models, TheoreticalABSTRACT
BACKGROUND: Barrett's oesophagus is a pre-malignant condition at gastroesophageal junction in which normal squamous epithelium is replaced by columnar shape epithelium, which predisposes oesophageal adenocarcinoma. It is known that Barrett's oesophagus evolves as a consequence of chronic gastro-oesophageal reflux disease. Although progression of Barrett's oesophagus to adenocarcinoma is still unclear, increasing incidence of oesophageal cancer and mortality worldwide make its study necessary. Several investigations have been made on the aetiology of oesophageal cancer. Most of them assessed genetical or environmental factors. However, potential role of bacteria in the development of oesophageal adenocarcinoma as a new environmental factor has not been addressed. Previous study on Barrett's disease detected presence of Campylobacter concisus as a new emerging pathogen on Barrett's and oesophageal cancer samples compared with healthy individuals. This indicates that this organism might involve in the progression of Barrett's to oesophageal adenocarcinoma. OBJECTIVES: This study aimed to determine the effects of C. concisus on expression of three biomarkers including interleukin-18 (IL-18), tumour necrosis factor-α (TNF-α) and tumour suppressor gene (p53) in three Barrett's cell lines. MATERIALS AND METHODS: Quantitative real-time PCR assays were developed to measure expression of pro-inflammatory mediators (IL-18 and TNF-α) and gene expression of p53 in Barrett's cell lines in co-culture with C. concisus. RESULTS: The mentioned organism was able to modulate considerably expression of p53, TNF-α and IL-18 in a time-dependent manner. CONCLUSIONS: The results showed that microorganism influences expression of carcinogenesis biomarker and cytokines in cell line models and possibility promotes oesophageal adenocarcinoma.
