Co-localisation of hypoxia and perfusion markers with parameters of glucose metabolism in human squamous cell carcinoma (hSCC) xenografts.
OBJECTIVE
To examine relationships between tumour hypoxia, perfusion and metabolic microenvironment at the microregional level in three different human squamous cell carcinomas (hSCC).


METHODS
Nude mice bearing FaDu, UT-SCC-15, and UT-SCC-5 hSCC were injected with pimonidazole hypoxia and Hoechst perfusion markers. Bioluminescence imaging was used to determine spatial distribution of glucose and lactate content in serial tumour sections. Metabolite levels were grouped in 10 concentration ranges. Images were co-registered and at each concentration range the proportion of area stained for pimonidazole and Hoechst was determined in 11-13 tumours per tumour line.


RESULTS
The spatial distribution of metabolites in pimonidazole hypoxic and Hoechst perfused areas is characterised by pronounced heterogeneity. In all three tumour lines glucose concentration decreased with increasing pimonidazole hypoxic fraction and increased with increasing perfused area at the microregional level. A weak albeit significant positive correlation between lactate concentration and pimonidazole hypoxic fraction was found only in UT-SCC-5. Lactate concentration consistently decreased with increasing perfused area in all three tumour lines.


CONCLUSIONS
Both glucose consumption and supply may contribute to the microregional glucose levels. Microregional lactate accumulation in tumours may be governed by clearance potential. The extent of microregional hypoxia cannot be predicted from the lactate concentration indicating that both parameters need to be measured independently.
Yaromina
Ala
A
Department of Radiation Oncology, OncoRay - Center for Radiation Research in Oncology, Medical Faculty C. G. Carus, Technische Universität, Dresden, Germany.
Quennet
Verena
V
Zips
Daniel
D
Meyer
Sandra
S
Shakirin
Georgy
G
Walenta
Stefan
S
Mueller-Klieser
Wolfgang
W
Baumann
Michael
M
D000818:Animals; D001562:Benzimidazoles / Q000493:pharmacokinetics; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D009593:Nitroimidazoles / Q000493:pharmacokinetics; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics; D014183:Transplantation, Heterologous
D001562:Benzimidazoles; D014408:Biomarkers, Tumor; D005456:Fluorescent Dyes; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D019344:Lactic Acid; C033815:pimonidazole; D005947:Glucose; C017807:bisbenzimide ethoxide trihydrochloride