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

Cell Physiol Biochem. 2010;26(2):147-54. doi: 10.1159/000320545. Epub 2010 Aug 24.

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.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis
  • Phosphoglycerate Kinase / genetics
  • Phosphoglycerate Kinase / metabolism*
  • Positron-Emission Tomography
  • Prognosis
  • Stomach Neoplasms / diagnostic imaging
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / pathology*

Substances

  • Pgk1 protein, mouse
  • Phosphoglycerate Kinase