Glycolytic metabolism and tumour response to fractionated irradiation.
OBJECTIVE
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.


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 6 weeks. 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.
Sattler
Ulrike G A
UG
Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
Meyer
Sandra S
SS
Quennet
Verena
V
Hoerner
Christian
C
Knoerzer
Hannah
H
Fabian
Christian
C
Yaromina
Ala
A
Zips
Daniel
D
Walenta
Stefan
S
Baumann
Michael
M
Mueller-Klieser
Wolfgang
W
D000255:Adenosine Triphosphate / Q000528:radiation effects*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy; D045744:Cell Line, Tumor; D019583:Dose Fractionation, Radiation; D005947:Glucose / Q000528:radiation effects*; D006019:Glycolysis; D006258:Head and Neck Neoplasms / Q000532:radiotherapy; D006801:Humans; D019344:Lactic Acid / Q000528:radiation effects*; D051379:Mice; D019289:Pyruvic Acid / Q000528:radiation effects*
D019344:Lactic Acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D005947:Glucose