title: Phosphoglycerate kinase 1 promoting tumor progression and metastasis in gastric cancer - detected in a tumor mouse model using positron emission tomography/magnetic resonance imaging.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of General, Visceral and Transplant Surgery, Comprehensive Cancer Center, University of Tuebingen, Tuebingen, Germany. derek.zieker@med.uni-tuebingen.de
authors.forename: Derek
authors.initials: D
authors.lastname: Zieker
authors.forename: Ingmar
authors.initials: I
authors.lastname: Königsrainer
authors.forename: Jürgen
authors.initials: J
authors.lastname: Weinreich
authors.forename: Stefan
authors.initials: S
authors.lastname: Beckert
authors.forename: Jörg
authors.initials: J
authors.lastname: Glatzle
authors.forename: Kay
authors.initials: K
authors.lastname: Nieselt
authors.forename: Sarah
authors.initials: S
authors.lastname: Bühler
authors.forename: Markus
authors.initials: M
authors.lastname: Löffler
authors.forename: Jochen
authors.initials: J
authors.lastname: Gaedcke
authors.forename: Hinnak
authors.initials: H
authors.lastname: Northoff
authors.forename: Julia G
authors.initials: JG
authors.lastname: Mannheim
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiehr
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Pichler
authors.forename: Claus
authors.initials: C
authors.lastname: von Weyhern
authors.forename: Björn L D M
authors.initials: BL
authors.lastname: Brücher
authors.forename: Alfred
authors.initials: A
authors.lastname: Königsrainer
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010735:Phosphoglycerate Kinase / Q000235:genetics / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011379:Prognosis; D013274:Stomach Neoplasms / Q000000981:diagnostic imaging / Q000201:enzymology / Q000473:pathology*
chemical_list: C528165:Pgk1 protein, mouse; D010735:Phosphoglycerate Kinase