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Volume 94, Issue 1, Pages 102-109 (January 2010)


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Glycolytic metabolism and tumour response to fractionated irradiation

Ulrike G.A. Sattlera1, Sandra S. Meyera1, Verena Quenneta2, Christian Hoernera, Hannah Knoerzera, Christian Fabiana, Ala Yarominab, Daniel Zipsb, Stefan Walentaa, Michael Baumannbcd, Wolfgang Mueller-KlieseraCorresponding Author Informationemail address

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.

a Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Germany

b Department of Radiation Oncology

c Experimental Centre and

d OncoRay-Centre for Radiation Research in Oncology, Technische Universität Dresden, Germany

Corresponding Author InformationCorresponding author. Address: Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Duesbergweg 6, 55128 Mainz, Germany.

1 Shared first authorship.

2 Present address: Radiation Biology and DNA Repair, Technische Universität, Darmstadt, Germany.

PII: S0167-8140(09)00646-X

doi:10.1016/j.radonc.2009.11.007


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