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130. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

30.04. - 03.05.2013, München

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Wnt5a Inhibits Proliferation and Invasion of Esophageal Adenocarcinoma Cells

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  • Orestis Lyros - Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Allgemein-, Viszeral- und Transplantationschirurgie, Mainz
  • Stefan Niebisch - Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Allgemein-, Viszeral- und Transplantationschirurgie, Mainz
  • Mary Otterson - Medical College of Wisconsin, Department of Surgery, Milwaukee, WI 53226
  • Tami Moore - Medical College of Wisconsin, Department of Surgery, Milwaukee, WI 53226
  • Hauke Lang - Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Allgemein-, Viszeral- und Transplantationschirurgie, Mainz
  • Ines Gockel - Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Allgemein-, Viszeral- und Transplantationschirurgie, Mainz
  • Reza Shaker - Medical College of Wisconsin, Division of Gastroenterology & Hepatology, Milwaukee, WI 53226
  • Parvaneh Rafiee - Medical College of Wisconsin, Department of Surgery, Milwaukee, WI 53226

Deutsche Gesellschaft für Chirurgie. 130. Kongress der Deutschen Gesellschaft für Chirurgie. München, 30.04.-03.05.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. Doc13dgch676

doi: 10.3205/13dgch676, urn:nbn:de:0183-13dgch6764

Published: April 26, 2013

© 2013 Lyros et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Introduction: The incidence of esophageal adenocarcinoma (EAC) has dramatically increased over the last decade while its prognosis remains still poor. The molecular mechanisms underlying the aggressive phenotype of EAC remain elusive. Wnt5a is classified as a non-transforming WNT family member whose role in carcinogenesis is still ambiguous. Wnt5a functions via ROR2 receptor and exhibits tumor suppressor activities in some cancers (thyroid, brain, breast and colorectal), but is aberrantly up-regulated in cancers of lung, stomach and prostate. Aim of the present study was to determine the role of Wnt5a/ROR2 signaling in EAC.

Material and methods: Human esophageal tissue from normal squamous mucosa, Barrett’s esophagus (BΕ) and esophageal adenocarcinoma were analyzed for ROR2 protein expression by Immunohistochemistry. Normal esophageal epithelial cell lines (EPC1-hTERT, EPC2-hTERT), a non-dysplastic columnar cell line derived from Barrett’s esophagus (CP-A) and an esophageal adenocarcinoma cancer cell line (OE33) were also utilized.Wnt5a gene and protein expression were determined by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively. The effect of Wnt5a on proliferation, survival and migration of OE33 cells was assessed after treatment with recombinant Wnt5a (rWnt5a) by [3H]-thymidine uptake assay, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and migration assay, respectively.

Results: ROR2 receptor was overexpressed while Wnt5a was downregulated in BE and EAC tissue compared to healthy squamous. Similar findings were found in CP-A and OE33 cells compared to normal epithelial cell lines.rWnt5a inhibited cell proliferation, survival and migration in a dose-dependent manner in OE33 cells (*P<0.05). Figure 1 [Fig. 1].

Conclusion: Dysregulation of Wnt5a/ROR2 signaling is characterizing EAC progression. Wnt5a demonstrates tumor suppression in OE33 cell line. Early loss of Wnt5a may contribute to the aggressive phenotype of EAC.