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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

01.12.2007 | Original article

Changes in glucose metabolism and gene expression after transfer of anti-angiogenic genes in rat hepatoma

verfasst von: Uwe Haberkorn, Johannes Hoffend, Kerstin Schmidt, Annette Altmann, Gabriel A. Bonaterra, Antonia Dimitrakopoulou-Strauss, Ludwig G. Strauss, Michael Eisenhut, Ralf Kinscherf

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 12/2007

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Abstract

Purpose

Human troponin I (TROP), the soluble receptor for vascular endothelial growth factor (sFLT) and angiostatin (ASTAT) are potent inhibitors of endothelial cell proliferation, angiogenesis and tumour growth in vivo. Transfer of these genes into tumours may induce changes not only in perfusion, but also more general ones such as changes in metabolism. The aim of this study was to assess these reactions using FDG-PET and high-throughput methods such as gene profiling.

Methods

We established Morris hepatoma (MH3924A) cell lines expressing TROP, sFLT or ASTAT and quantified ¹⁸F-fluorodeoxyglucose (¹⁸FDG) uptake by dynamic positron emission tomography (PET) after tumour inoculation in ACI rats. Furthermore, expression of glucose transporter-1 and -3 (GLUT-1 and GLUT-3) as well as hexokinase-1 and -2 were investigated by RT-PCR and immunohistomorphometry. In addition, gene array analyses were performed.

Results

¹⁸FDG uptake, vascular fraction and distribution volume were significantly higher in all genetically modified tumours. Immunohistomorphometry showed an increased percentage of hexokinase-1 and -2 as well as GLUT-1 and -3 immunoreactive (ir) cells. Using gene arrays and comparing all three groups of genetically modified tumours, we found upregulated expression of 36 genes related to apoptosis, signal transduction, stress or metabolism.

Conclusion

TROP-, sFLT- or ASTAT-expressing MH3924A tumours show enhanced influx of ¹⁸FDG, which seems to be caused by several factors: enhanced exchange of nutrients between blood and tumour, increased amounts of glucose transporters and hexokinases, and increased expression of genes related to apoptosis, matrix and stress, which induce an increased demand for glucose.

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Titel: Changes in glucose metabolism and gene expression after transfer of anti-angiogenic genes in rat hepatoma
verfasst von: Uwe Haberkorn
Johannes Hoffend
Kerstin Schmidt
Annette Altmann
Gabriel A. Bonaterra
Antonia Dimitrakopoulou-Strauss
Ludwig G. Strauss
Michael Eisenhut
Ralf Kinscherf
Publikationsdatum: 01.12.2007
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 12/2007
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-007-0520-4

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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