In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett’s sequence
Abstract Background An altered Wnt-signaling activation has been reported during Barrett’s esophagus progression, but with rarely detected mutations in APC and β-catenin (CTNNB1) genes. Methods In this study, a robust in-depth expression pattern analysis of frizzled receptors, co-receptors, the Wnt-...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | BMC Gastroenterology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12876-019-0957-5 |
| _version_ | 1828894314939285504 |
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| author | Katharina Götzel Olga Chemnitzer Luisa Maurer Arne Dietrich Uwe Eichfeld Orestis Lyros Yusef Moulla Stefan Niebisch Matthias Mehdorn Boris Jansen-Winkeln Michael Vieth Albrecht Hoffmeister Ines Gockel René Thieme |
| author_facet | Katharina Götzel Olga Chemnitzer Luisa Maurer Arne Dietrich Uwe Eichfeld Orestis Lyros Yusef Moulla Stefan Niebisch Matthias Mehdorn Boris Jansen-Winkeln Michael Vieth Albrecht Hoffmeister Ines Gockel René Thieme |
| author_sort | Katharina Götzel |
| collection | DOAJ |
| description | Abstract Background An altered Wnt-signaling activation has been reported during Barrett’s esophagus progression, but with rarely detected mutations in APC and β-catenin (CTNNB1) genes. Methods In this study, a robust in-depth expression pattern analysis of frizzled receptors, co-receptors, the Wnt-ligands Wnt3a and Wnt5a, the Wnt-signaling downstream targets Axin2, and CyclinD1, as well as the activation of the intracellular signaling kinases Akt and GSK3β was performed in an in vitro cell culture model of Barrett’s esophagus. Representing the Barrett’s sequence, we used normal esophageal squamous epithelium (EPC-1, EPC-2), metaplasia (CP-A) and dysplasia (CP-B) to esophageal adenocarcinoma (EAC) cell lines (OE33, OE19) and primary specimens of squamous epithelium, metaplasia and EAC. Results A loss of Wnt3a expression was observed beginning from the metaplastic cell line CP-A towards dysplasia (CP-B) and EAC (OE33 and OE19), confirmed by a lower staining index of WNT3A in Barrett’s metaplasia and EAC, than in squamous epithelium specimens. Frizzled 1–10 expression analysis revealed a distinct expression pattern, showing the highest expression for Fzd2, Fzd3, Fzd4, Fzd5, Fzd7, and the co-receptor LRP5/6 in EAC cells, while Fzd3 and Fzd7 were rarely expressed in primary specimens from squamous epithelium. Conclusion Despite the absence of an in-depth characterization of Wnt-signaling-associated receptors in Barrett’s esophagus, by showing variations of the Fzd- and co-receptor profiles, we provide evidence to have a significant role during Barrett’s progression and the underlying pathological mechanisms. |
| first_indexed | 2024-12-13T14:08:17Z |
| format | Article |
| id | doaj.art-6994bb9d44594a49b23842c979dc5ced |
| institution | Directory Open Access Journal |
| issn | 1471-230X |
| language | English |
| last_indexed | 2024-12-13T14:08:17Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Gastroenterology |
| spelling | doaj.art-6994bb9d44594a49b23842c979dc5ced2022-12-21T23:42:32ZengBMCBMC Gastroenterology1471-230X2019-03-0119111210.1186/s12876-019-0957-5In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett’s sequenceKatharina Götzel0Olga Chemnitzer1Luisa Maurer2Arne Dietrich3Uwe Eichfeld4Orestis Lyros5Yusef Moulla6Stefan Niebisch7Matthias Mehdorn8Boris Jansen-Winkeln9Michael Vieth10Albrecht Hoffmeister11Ines Gockel12René Thieme13Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of LeipzigDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of LeipzigDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of LeipzigDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of LeipzigDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of LeipzigDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of LeipzigDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of LeipzigDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of LeipzigDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of LeipzigDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of LeipzigInstitute for Pathology, Klinikum BayreuthDepartment of Gastroenterology and Rheumatology, University Hospital of LeipzigDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of LeipzigDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of LeipzigAbstract Background An altered Wnt-signaling activation has been reported during Barrett’s esophagus progression, but with rarely detected mutations in APC and β-catenin (CTNNB1) genes. Methods In this study, a robust in-depth expression pattern analysis of frizzled receptors, co-receptors, the Wnt-ligands Wnt3a and Wnt5a, the Wnt-signaling downstream targets Axin2, and CyclinD1, as well as the activation of the intracellular signaling kinases Akt and GSK3β was performed in an in vitro cell culture model of Barrett’s esophagus. Representing the Barrett’s sequence, we used normal esophageal squamous epithelium (EPC-1, EPC-2), metaplasia (CP-A) and dysplasia (CP-B) to esophageal adenocarcinoma (EAC) cell lines (OE33, OE19) and primary specimens of squamous epithelium, metaplasia and EAC. Results A loss of Wnt3a expression was observed beginning from the metaplastic cell line CP-A towards dysplasia (CP-B) and EAC (OE33 and OE19), confirmed by a lower staining index of WNT3A in Barrett’s metaplasia and EAC, than in squamous epithelium specimens. Frizzled 1–10 expression analysis revealed a distinct expression pattern, showing the highest expression for Fzd2, Fzd3, Fzd4, Fzd5, Fzd7, and the co-receptor LRP5/6 in EAC cells, while Fzd3 and Fzd7 were rarely expressed in primary specimens from squamous epithelium. Conclusion Despite the absence of an in-depth characterization of Wnt-signaling-associated receptors in Barrett’s esophagus, by showing variations of the Fzd- and co-receptor profiles, we provide evidence to have a significant role during Barrett’s progression and the underlying pathological mechanisms.http://link.springer.com/article/10.1186/s12876-019-0957-5Barrett’s esophagusEsophageal adenocarcinomaWnt-signalingFrizzled receptorsWnt3a |
| spellingShingle | Katharina Götzel Olga Chemnitzer Luisa Maurer Arne Dietrich Uwe Eichfeld Orestis Lyros Yusef Moulla Stefan Niebisch Matthias Mehdorn Boris Jansen-Winkeln Michael Vieth Albrecht Hoffmeister Ines Gockel René Thieme In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett’s sequence BMC Gastroenterology Barrett’s esophagus Esophageal adenocarcinoma Wnt-signaling Frizzled receptors Wnt3a |
| title | In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett’s sequence |
| title_full | In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett’s sequence |
| title_fullStr | In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett’s sequence |
| title_full_unstemmed | In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett’s sequence |
| title_short | In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett’s sequence |
| title_sort | in depth characterization of the wnt signaling β catenin pathway in an in vitro model of barrett s sequence |
| topic | Barrett’s esophagus Esophageal adenocarcinoma Wnt-signaling Frizzled receptors Wnt3a |
| url | http://link.springer.com/article/10.1186/s12876-019-0957-5 |
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