Impact of Deoxycholic Acid on Oesophageal Adenocarcinoma Invasion: Effect on Matrix Metalloproteinases
Bile acids (BAs) have been implicated in the development of oesophagitis, Barrett’s oesophagus and oesophageal adenocarcinoma (OAC). However, whether BAs promote cancer invasiveness has not been elucidated. We evaluated the role of BAs, in particular deoxycholic acid (DCA), in OAC invasion. Migratio...
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/21/8042 |
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| author | Fran Quilty Anne-Marie Byrne John Aird Sheeren El Mashad Adolfo Parra-Blanco Aideen Long John F Gilmer Carlos Medina |
| author_facet | Fran Quilty Anne-Marie Byrne John Aird Sheeren El Mashad Adolfo Parra-Blanco Aideen Long John F Gilmer Carlos Medina |
| author_sort | Fran Quilty |
| collection | DOAJ |
| description | Bile acids (BAs) have been implicated in the development of oesophagitis, Barrett’s oesophagus and oesophageal adenocarcinoma (OAC). However, whether BAs promote cancer invasiveness has not been elucidated. We evaluated the role of BAs, in particular deoxycholic acid (DCA), in OAC invasion. Migration and invasiveness in untreated and BA-treated oesophageal SKGT-4 cancer cells were evaluated. Activity and expression of different matrix metalloproteinases (MMPs) were determined by zymography, ELISA, PCR and Western blot. Finally, human OAC tissues were stained for MMP-10 by immunohistochemistry. It was found that SKGT-4 cells incubated with low concentrations of DCA had a significant increase in invasion. In addition, MMP-10 mRNA and protein expression were also increased in the presence of DCA. MMP-10 was found to be highly expressed both in-vitro and in-vivo in neoplastic OAC cells relative to non-neoplastic squamous epithelial cells. Our results show that DCA promotes OAC invasion and MMP-10 overexpression. This study will advance our understanding of the pathophysiological mechanisms involved in human OAC and shows promise for the development of new therapeutic strategies. |
| first_indexed | 2024-03-10T15:16:01Z |
| format | Article |
| id | doaj.art-9fdc4fa8a0004d9795fce67d9c325087 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:16:01Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9fdc4fa8a0004d9795fce67d9c3250872023-11-20T18:54:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012121804210.3390/ijms21218042Impact of Deoxycholic Acid on Oesophageal Adenocarcinoma Invasion: Effect on Matrix MetalloproteinasesFran Quilty0Anne-Marie Byrne1John Aird2Sheeren El Mashad3Adolfo Parra-Blanco4Aideen Long5John F Gilmer6Carlos Medina7School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, 2 Dublin, IrelandSchool of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, 2 Dublin, IrelandDepartment of Histopathology and Morbid Anatomy, School of Medicine, Trinity College Dublin, 2 Dublin, IrelandCork Cancer Research Centre, BioSciences Institute, University College, T12 YN60 Cork, IrelandDepartment of Gastroenterology, NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG11 8NF, UKSchool of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Trinity Centre for Health Sciences, St James’s Hospital, 8 Dublin, IrelandSchool of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, 2 Dublin, IrelandSchool of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, 2 Dublin, IrelandBile acids (BAs) have been implicated in the development of oesophagitis, Barrett’s oesophagus and oesophageal adenocarcinoma (OAC). However, whether BAs promote cancer invasiveness has not been elucidated. We evaluated the role of BAs, in particular deoxycholic acid (DCA), in OAC invasion. Migration and invasiveness in untreated and BA-treated oesophageal SKGT-4 cancer cells were evaluated. Activity and expression of different matrix metalloproteinases (MMPs) were determined by zymography, ELISA, PCR and Western blot. Finally, human OAC tissues were stained for MMP-10 by immunohistochemistry. It was found that SKGT-4 cells incubated with low concentrations of DCA had a significant increase in invasion. In addition, MMP-10 mRNA and protein expression were also increased in the presence of DCA. MMP-10 was found to be highly expressed both in-vitro and in-vivo in neoplastic OAC cells relative to non-neoplastic squamous epithelial cells. Our results show that DCA promotes OAC invasion and MMP-10 overexpression. This study will advance our understanding of the pathophysiological mechanisms involved in human OAC and shows promise for the development of new therapeutic strategies.https://www.mdpi.com/1422-0067/21/21/8042deoxycholic acidmatrix metalloproteinasesmmp-10oesophageal adenocarcinoma |
| spellingShingle | Fran Quilty Anne-Marie Byrne John Aird Sheeren El Mashad Adolfo Parra-Blanco Aideen Long John F Gilmer Carlos Medina Impact of Deoxycholic Acid on Oesophageal Adenocarcinoma Invasion: Effect on Matrix Metalloproteinases International Journal of Molecular Sciences deoxycholic acid matrix metalloproteinases mmp-10 oesophageal adenocarcinoma |
| title | Impact of Deoxycholic Acid on Oesophageal Adenocarcinoma Invasion: Effect on Matrix Metalloproteinases |
| title_full | Impact of Deoxycholic Acid on Oesophageal Adenocarcinoma Invasion: Effect on Matrix Metalloproteinases |
| title_fullStr | Impact of Deoxycholic Acid on Oesophageal Adenocarcinoma Invasion: Effect on Matrix Metalloproteinases |
| title_full_unstemmed | Impact of Deoxycholic Acid on Oesophageal Adenocarcinoma Invasion: Effect on Matrix Metalloproteinases |
| title_short | Impact of Deoxycholic Acid on Oesophageal Adenocarcinoma Invasion: Effect on Matrix Metalloproteinases |
| title_sort | impact of deoxycholic acid on oesophageal adenocarcinoma invasion effect on matrix metalloproteinases |
| topic | deoxycholic acid matrix metalloproteinases mmp-10 oesophageal adenocarcinoma |
| url | https://www.mdpi.com/1422-0067/21/21/8042 |
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