Literature DB >> 20798498

Phosphoglycerate kinase 1 promoting tumor progression and metastasis in gastric cancer - detected in a tumor mouse model using positron emission tomography/magnetic resonance imaging.

Derek Zieker1, Ingmar Königsrainer, Jürgen Weinreich, Stefan Beckert, Jörg Glatzle, Kay Nieselt, Sarah Bühler, Markus Löffler, Jochen Gaedcke, Hinnak Northoff, Julia G Mannheim, Stefan Wiehr, Bernd J Pichler, Claus von Weyhern, Björn L D M Brücher, Alfred Königsrainer.   

Abstract

BACKGROUND/AIMS: Tumor dissemination is frequent in gastric cancer and implies a poor prognosis. Cure is only achievable provided an accurate staging is performed at primary diagnosis. In previous studies we were able to show a relevant impact of increased phosphoglycerate kinase 1 expression (PGK1; a glycolytic enzyme) on invasive properties of gastric cancer in-vivo and in-vitro. Thus the aim of the present study was to evaluate the effect of enhanced PGK1 expression in gastric cancer employing magnetic resonance (MR)-imaging combined with positron emission tomography (PET), a recently emerging new high resolution imaging technique in a mouse model.
METHODS: A metastatic nude mouse model simulating human gastric cancer behavior by orthotopic tumor implantation was established. Mice were divided into one control group (n=5) and two experimental groups (n=30) divided by half in animals baring tumors from MKN45-cells and MKN45-cells with plasmid-mediated overexpression of PGK1. In the course of tumor growth MR-imaging and PET/MRI fusion was performed. Successively experimental animals were examined macroscopically and histopathologically regarding growth, metastasis and PGK1 expression.
RESULTS: Elevated PGK1 expression increased invasive and metastatic behavior of implanted gastric tumors significantly. MR/PET- imaging results in-vivoand subsequent ex-vivo findings concerning tumor growth and metastasis correlated excellently and could be underlined by concordant immuohistochemical PGK1 staining.
CONCLUSION: Consistent in-vivo findings suggest that PGK1 might be crucially involved in gastric malignancy regarding growth and metastasis, which was also underlined by novel imaging techniques. Thus, PGK1 may be exploited as a prognostic marker and/or be of potential therapeutic value preventing malignant dissemination. Copyright 2010 S. Karger AG, Basel.

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Year:  2010        PMID: 20798498     DOI: 10.1159/000320545

Source DB:  PubMed          Journal:  Cell Physiol Biochem        ISSN: 1015-8987


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