Bile accelerates carcinogenic processes in pancreatic ductal adenocarcinoma cells through the overexpression of MUC4

Abstract Pancreatic cancer (PC) is one of the leading causes of mortality rate globally and is usually associated with obstructive jaundice (OJ). Up to date, there is no clear consensus on whether biliary decompression should be performed prior to surgery and how high levels of serum bile affects th...

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Autores principales:	Eleonóra Gál, Zoltán Veréb, Lajos Kemény, Dávid Rakk, András Szekeres, Eszter Becskeházi, László Tiszlavicz, Tamás Takács, László Czakó, Péter Hegyi, Viktória Venglovecz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/82969a9d169e414b9c1e34b0ea6bac25
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spelling	oai:doaj.org-article:82969a9d169e414b9c1e34b0ea6bac252021-12-02T13:58:15ZBile accelerates carcinogenic processes in pancreatic ductal adenocarcinoma cells through the overexpression of MUC410.1038/s41598-020-79181-62045-2322https://doaj.org/article/82969a9d169e414b9c1e34b0ea6bac252020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79181-6https://doaj.org/toc/2045-2322Abstract Pancreatic cancer (PC) is one of the leading causes of mortality rate globally and is usually associated with obstructive jaundice (OJ). Up to date, there is no clear consensus on whether biliary decompression should be performed prior to surgery and how high levels of serum bile affects the outcome of PC. Therefore, our study aims were to characterise the effect of bile acids (BAs) on carcinogenic processes using pancreatic ductal adenocarcinoma (PDAC) cell lines and to investigate the underlying mechanisms. Liquid chromatography-mass spectrometry was used to determine the serum concentrations of BAs. The effects of BAs on tumour progression were investigated using different assays. Mucin expressions were studied in normal and PDAC cell lines and in human samples at gene and protein levels and results were validated with gene silencing. The levels of BAs were significantly higher in the PDAC + OJ group compared to the healthy control. Treating PDAC cells with different BAs or with human serum obtained from PDAC + OJ patients enhanced the rate of proliferation, migration, adhesion, colony forming, and the expression of MUC4. In PDAC + OJ patients, MUC4 expression was higher and the 4-year survival rate was lower compare to PDAC patients. Silencing of MUC4 decreased BAs-induced carcinogenic processes in PDAC cells. Our results show that BAs promote carcinogenic process in PDAC cells, in which the increased expression of MUC4 plays an important role. Based on these results, we assume that in PC patients, where the disease is associated with OJ, the early treatment of biliary obstruction improves life expectancy.Eleonóra GálZoltán VerébLajos KeményDávid RakkAndrás SzekeresEszter BecskeháziLászló TiszlaviczTamás TakácsLászló CzakóPéter HegyiViktória VengloveczNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-16 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eleonóra Gál Zoltán Veréb Lajos Kemény Dávid Rakk András Szekeres Eszter Becskeházi László Tiszlavicz Tamás Takács László Czakó Péter Hegyi Viktória Venglovecz Bile accelerates carcinogenic processes in pancreatic ductal adenocarcinoma cells through the overexpression of MUC4
description	Abstract Pancreatic cancer (PC) is one of the leading causes of mortality rate globally and is usually associated with obstructive jaundice (OJ). Up to date, there is no clear consensus on whether biliary decompression should be performed prior to surgery and how high levels of serum bile affects the outcome of PC. Therefore, our study aims were to characterise the effect of bile acids (BAs) on carcinogenic processes using pancreatic ductal adenocarcinoma (PDAC) cell lines and to investigate the underlying mechanisms. Liquid chromatography-mass spectrometry was used to determine the serum concentrations of BAs. The effects of BAs on tumour progression were investigated using different assays. Mucin expressions were studied in normal and PDAC cell lines and in human samples at gene and protein levels and results were validated with gene silencing. The levels of BAs were significantly higher in the PDAC + OJ group compared to the healthy control. Treating PDAC cells with different BAs or with human serum obtained from PDAC + OJ patients enhanced the rate of proliferation, migration, adhesion, colony forming, and the expression of MUC4. In PDAC + OJ patients, MUC4 expression was higher and the 4-year survival rate was lower compare to PDAC patients. Silencing of MUC4 decreased BAs-induced carcinogenic processes in PDAC cells. Our results show that BAs promote carcinogenic process in PDAC cells, in which the increased expression of MUC4 plays an important role. Based on these results, we assume that in PC patients, where the disease is associated with OJ, the early treatment of biliary obstruction improves life expectancy.
format	article
author	Eleonóra Gál Zoltán Veréb Lajos Kemény Dávid Rakk András Szekeres Eszter Becskeházi László Tiszlavicz Tamás Takács László Czakó Péter Hegyi Viktória Venglovecz
author_facet	Eleonóra Gál Zoltán Veréb Lajos Kemény Dávid Rakk András Szekeres Eszter Becskeházi László Tiszlavicz Tamás Takács László Czakó Péter Hegyi Viktória Venglovecz
author_sort	Eleonóra Gál
title	Bile accelerates carcinogenic processes in pancreatic ductal adenocarcinoma cells through the overexpression of MUC4
title_short	Bile accelerates carcinogenic processes in pancreatic ductal adenocarcinoma cells through the overexpression of MUC4
title_full	Bile accelerates carcinogenic processes in pancreatic ductal adenocarcinoma cells through the overexpression of MUC4
title_fullStr	Bile accelerates carcinogenic processes in pancreatic ductal adenocarcinoma cells through the overexpression of MUC4
title_full_unstemmed	Bile accelerates carcinogenic processes in pancreatic ductal adenocarcinoma cells through the overexpression of MUC4
title_sort	bile accelerates carcinogenic processes in pancreatic ductal adenocarcinoma cells through the overexpression of muc4
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/82969a9d169e414b9c1e34b0ea6bac25
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Bile accelerates carcinogenic processes in pancreatic ductal adenocarcinoma cells through the overexpression of MUC4

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