Phosphoglycerate kinase 1 promoting tumor progression and metastasis in gastric cancer - detected in a tumor mouse model using positron emission tomography/magnetic resonance imaging.
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.
Zieker
Derek
D
Department of General, Visceral and Transplant Surgery, Comprehensive Cancer Center, University of Tuebingen, Tuebingen, Germany. derek.zieker@med.uni-tuebingen.de
Königsrainer
Ingmar
I
Weinreich
Jürgen
J
Beckert
Stefan
S
Glatzle
Jörg
J
Nieselt
Kay
K
Bühler
Sarah
S
Löffler
Markus
M
Gaedcke
Jochen
J
Northoff
Hinnak
H
Mannheim
Julia G
JG
Wiehr
Stefan
S
Pichler
Bernd J
BJ
von Weyhern
Claus
C
Brücher
Björn L D M
BL
Königsrainer
Alfred
A
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*
C528165:Pgk1 protein, mouse; D010735:Phosphoglycerate Kinase