MMP-1 is a (pre-)invasive factor in Barrett-associated esophageal adenocarcinomas and is associated with positive lymph node status

Journal of Translational Medicine

Research

Maria Lazariotou¹  Christoph Otto²  Martin Grimm²  Luisa Stuermer²  Christoph T Germer²  Christoph Reiber²  Burkhard HA von Rahden²  Andreas Höfelmayr²  Stefan Gattenlöhner³  Stefan Kircher⁴ 

[1] Department of Cardiac and Thoracic Surgery, University of Wuerzburg Hospital, Oberduerrbacher Strasse 6, 97080, Wuerzburg, Germany;Department of General-, Visceral-, Vascular and Pediatric Surgery, University of Wuerzburg Hospital, Oberduerrbacher Strasse 6, 97080, Wuerzburg, Germany;Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036, Graz, Austria;Institute of Pathology, University of Wuerzburg, Josef-Schneider Strasse 2, 97080, Wuerzburg, Germany;

关键词: Intestinal Metaplasia;    Intraepithelial Neoplasia;    Esophageal Adenocarcinoma;    Cancer Stem Cell Hypothesis;    Multistep Carcinogenesis;   

DOI  :  10.1186/1479-5876-8-99

 received in 2010-06-21, accepted in 2010-10-14,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundEsophageal adenocarcinomas (EACs) arise due to gastroesophageal reflux, with Barrett's esophagus (BE) regarded as precancerous lesion. Matrix metalloproteinases (MMPs) might play a role during the multistep carcinogenetic process.MethodsExpression of MMP-1 and -13 was analyzed in esophageal cancer (n = 41 EAC with BE, n = 19 EAC without BE, and n = 10 esophageal squamous-cell carcinomas, ESCC), furthermore in BE without intraepithelial neoplasia (IN) (n = 18), and the cell line OE-33. MMP-1 was co-labelled with Ki-67 (proliferation), Cdx-2 (marker for intestinal metaplasia, BE) and analyzed on mRNA level. MMP-1 staining results were correlated with clinicopatholocical parameters.ResultsOn protein level, MMP-1 expression was found in 39 of 41 (95%) EAC with BE, in 19 of 19 (100%) EAC without BE, in 6 of 10 (60%) ESCC, and in 10 of 18 (56%) BE without IN. No expression of MMP-13 was found in these specimens. Quantification showed 48% MMP-1 positive cells in EAC with BE, compared to 35% in adjacent BE (p < 0.05), 44% in EAC without BE, 32% in ESCC, and 4% in BE without IN. Immunofluorescence double staining experiments revealed increased MMP-1 expressing in proliferating cells (MMP-1+/Ki-67+) (r = 0.943 for BE and r = 0.811 for EAC). On mRNA-level, expression of MMP-1 was significantly higher in EAC compared to BE (p = 0.01) and confirmed immunohistochemical staining results. High MMP-1 levels were associated with lymph node metastases but not with poorer survival (p = 0.307).ConclusionsOur findings suggest that MMP-1 plays a role as preinvasive factor in BE-associated EAC. Expression of MMP-1 in proliferating BE and EAC cells suggest malignant proliferation following the clonal expansion model.

【 授权许可】

Unknown   
© Grimm et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.