Bile acids: a potential role in the pathogenesis of pharyngeal malignancy
| Autor: | Bernard Verdon, Michael W. Mather, Vinidh Paleri, Chris Ward, Janet A. Wilson, Zachary Shellman, Adil Aldhahrani, Jason Powell, Jeffrey P. Pearson |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Epithelial-Mesenchymal Transition Cell Culture Techniques Bile Acids and Salts Transforming Growth Factor beta1 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Gastrointestinal Agents Chenodeoxycholic acid Tumor Cells Cultured medicine Humans Epithelial–mesenchymal transition Viability assay Gastrointestinal agent Hypopharyngeal Neoplasms business.industry Deoxycholic acid Cholic acid Squamous carcinoma 030104 developmental biology Matrix Metalloproteinase 9 Otorhinolaryngology chemistry Cell culture 030220 oncology & carcinogenesis Carcinoma Squamous Cell Cancer research business |
| Zdroj: | Clinical Otolaryngology. 42:969-973 |
| ISSN: | 1749-4478 |
| DOI: | 10.1111/coa.12822 |
| Popis: | Objective Gastro-oesophageal reflux disease is thought to be a risk factor for head and neck malignancies. Bile acids are one of the principle components of gastric refluxate and have previously been implicated in the development of oesophageal and bowel malignancies. There is clear evidence that bile acids reflux into the laryngopharynx. Despite this, the carcinogenic properties of bile acids in this area are yet to be fully identified. We therefore investigated the potential role of bile acids in pharyngeal malignancy, through the highly conserved process of epithelial–mesenchymal transition (EMT). EMT occurs in invasion and metastasis and is a central process in the development of epithelial carcinoma. Design Translational research study. Methods Human hypopharyngeal squamous carcinoma FaDu cells were challenged with primary (cholic or chenodeoxycholic) and secondary (deoxycholic or lithocholic) bile acids. EMT-relevant proteins TGF-β1 and MMP-9 were measured in the cell culture supernates at 48 h via ELISA. Cell viability was confirmed >95% via CellTiter-Blue assay. Results Significantly greater concentrations of TGF-β1 were measured in the culture supernates of cells treated with cholic acid, deoxycholic acid and chenodeoxycholic acid. MMP-9 levels were increased in deoxycholic acid and lithocolic acid stimulations when compared to control (P < 0.05). Conclusion This is the first demonstration that bile acids induce TGF-β1 and MMP-9 in pharyngeal cells. TGF-β1 is considered a master switch for EMT, while MMP-9 is a part of the EMT proteome which degrades basement membranes. This implies a potential role for bile acids in pharyngeal carcinogenesis through the mechanism of EMT and suggests potential novel therapeutic targets. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |