Glycolytic metabolism and tumour response to fractionated irradiation

Sattler, Ulrike G.A.; Meyer, Sandra S.; Quennet, Verena; Hoerner, Christian; Knoerzer, Hannah; Fabian, Christian; Yaromina, Ala; Zips, Daniel; Walenta, Stefan; Baumann, Michael; Mueller-Klieser, Wolfgang

doi:10.1016/j.radonc.2009.11.007

« Previous Next »Radiotherapy & Oncology
Volume 94, Issue 1 , Pages 102-109, January 2010

Glycolytic metabolism and tumour response to fractionated irradiation

Ulrike G.A. Sattler
- Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Germany
- Shared first authorship.
Sandra S. Meyer
- Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Germany
- Shared first authorship.
Verena Quennet
- Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Germany
- Present address: Radiation Biology and DNA Repair, Technische Universität, Darmstadt, Germany.
Christian Hoerner
- Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Germany
Hannah Knoerzer
- Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Germany
Christian Fabian
- Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Germany
Ala Yaromina
- Department of Radiation Oncology
Daniel Zips
- Department of Radiation Oncology
Stefan Walenta
- Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Germany
Michael Baumann
- Department of Radiation Oncology
- Experimental Centre and
- OncoRay-Centre for Radiation Research in Oncology, Technische Universität Dresden, Germany
Wolfgang Mueller-Klieser
- Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Germany
- Corresponding author. Address: Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Duesbergweg 6, 55128 Mainz, Germany.

Received 26 June 2009; received in revised form 18 September 2009; accepted 4 November 2009. published online 28 December 2009.

Abstract

Background and purpose

To study whether pre-therapeutic lactate or pyruvate predict for tumour response to fractionated irradiation and to identify possible coherencies between intermediates of glycolysis and expression levels of selected proteins.

Materials and methods

Concentrations of lactate, pyruvate, glucose and ATP were quantified via bioluminescence imaging in tumour xenografts derived from 10 human head and neck squamous cell carcinoma (HNSCC) lines. Tumours were irradiated with 30 fractions within 6weeks. Expression levels of the selected proteins in tumours were measured at the mRNA and protein level. Tumour-infiltrating leucocytes were quantified after staining for CD45.

Results

Lactate but not pyruvate concentrations were significantly correlated with tumour response to fractionated irradiation. Lactate concentrations in vivo did not reflect lactate production rates in vitro. Metabolite concentrations did not correlate with GLUT1, PFK-L or LDH-A at the transcriptional or protein level. CD45-positive cell infiltration was low in the majority of tumours and did not correlate with lactate concentration.

Conclusions

Our data support the hypothesis that the antioxidative capacity of lactate may contribute to radioresistance in malignant tumours. Non-invasive imaging of lactate to monitor radiation response and testing inhibitors of glycolysis to improve outcome after fractionated radiotherapy warrant further investigations.

Keywords: Metabolic bioluminescence imaging, Human tumour xenograft, Fractionated irradiation, Local tumour control, Tumour glycolysis, Human head and neck squamous cell carcinomas