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Disintegrin and metalloproteinases (ADAMs) expression in gastroesophageal reflux disease and in esophageal adenocarcinoma

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Abstract

Background

Clinically useful marker molecules for the progression of gastroesophageal reflux disease and Barrett’s esophagus (BE) to esophageal adenocarcinoma (EAC) are lacking. Many adenocarcinomas and inflammatory conditions exhibit increased expression of ADAMs, ‘a disintegrin and metalloproteinases’.

Methods

We assessed the expression of five ADAMs (9, 10, 12, 17, 19) in three esophageal cell lines (Het-1A, OE19, OE33) by RT-PCR and Western blotting, and in human samples of normal esophagus, esophagitis, BE, Barrett’s dysplasia, and EAC by RT-PCR, and in selected samples by immunohistochemistry.

Results

EAC patients showed increased mRNA expression of ADAMs 9, 12, 17 and 19, as compared to controls. At immunohistochemistry, ADAM9 and ADAM10 proteins were increased in EAC. Patient samples also showed increased mRNA expression of ADAM12 in esophagitis, of ADAM9 in BE, and of ADAMs 9, 12 and 19 in Barrett’s dysplasia, as compared to controls. Two EAC cell lines showed increased ADAM9 mRNA.

Conclusions

ADAM9 expression is increased in EAC. Its predecessors show increased ADAM9 mRNA expression. The importance of the alterations in ADAM expression for the development of EAC, and their use as marker molecules, warrant further studies.

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Acknowledgments

The authors wish to thank doctors Eero Sihvo, Juha Kauppi, Tarja Peräkylä and Perttu Arkkila for their invaluable assistance in providing part of the patient samples in the General Thoracic and Esophageal Surgery clinic, Heart and Lung Centre, Helsinki University Hospital, and in the Department of Gastroenterology, Helsinki University Hospital. The authors also wish to thank Mrs. Yvonne Sundström for her skilful technical and secretarial assistance. The authors did not receive any writing assistance.

Funding

The study was financially supported by grants from the Sigrid Jusélius Foundation (no grant number) and Helsinki University Hospital Research Funds (TYH 2012131 and TYH 2014240).

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Authors and Affiliations

  1. Department of General Thoracic and Esophageal Surgery, Heart and Lung Centre, Helsinki University Hospital, Helsinki, Finland

    T. Kauttu, I. Ilonen, J. Räsänen & J. Salo

  2. Department of Surgery, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland

    T. Kauttu, H. Mustonen, I. Ilonen, J. Räsänen, J. Salo & P. Puolakkainen

  3. Department of Gastroenterologic and General Surgery, Helsinki University Hospital, Haartmaninkatu 4, PO Box 340, 00290, Helsinki, Finland

    H. Mustonen, S. Vainionpää & P. Puolakkainen

  4. Department of Pathology, HUSLAB, Helsinki University Hospital, Helsinki, Finland

    L. Krogerus

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  1. T. Kauttu
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Correspondence to P. Puolakkainen.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Kauttu, T., Mustonen, H., Vainionpää, S. et al. Disintegrin and metalloproteinases (ADAMs) expression in gastroesophageal reflux disease and in esophageal adenocarcinoma. Clin Transl Oncol 19, 58–66 (2017). https://doi.org/10.1007/s12094-016-1503-3

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  • DOI: https://doi.org/10.1007/s12094-016-1503-3

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