Metabolic and proteomic differentials in head and neck squamous cell carcinomas and normal gingival tissue.
OBJECTIVE
A high lactate content in malignant head and neck cancer (Head and neck squamous cell carcinomas, HNSCC) is associated with a higher risk of metastatic spread and lower overall patient survival. However, until present, the underlying mechanisms are not clearly understood. Here, a systematic comparison of glucose metabolism in HNSCC and homologous normal tissue is presented for the first time.


METHODS
The concentrations of glucose, lactate and ATP were measured in cryobiopsies of 29 human HNSCC and of 9 normal mucosa using bioluminescence imaging. The protein expression of lactate dehydrogenase (LDH) was analyzed by Western blotting.


RESULTS
Tumors own a higher content of lactate and LDH in comparison with normal tissues. However, within the tumor group, the grade of LDH expression shows substantially strong variation and overlap with normal values. Furthermore, LDH expression was not correlated with tumor lactate content. Investigating a small subpopulation, patients with a short-term survival had significantly higher tumor lactate levels compared to patients with long-term survival.


CONCLUSIONS
The data provide clear evidence of an enhanced glycolysis in tumors compared to normal tissue. This may partially but not completely attributable to an elevated expression of LDH. High tumor lactate levels may be predictive for restricted patient survival. In conclusion, lactate measurements, for example non-invasively with MRT, should be advanced for use in clinical routine as a supportive tool for tumor diagnosis and prognosis.
Ziebart
Thomas
T
Department of Oral and Maxillofacial Surgery, University Medical Center of the Johannes Gutenberg-University of Mainz, 55131 Mainz, Germany.
Walenta
Stefan
S
Kunkel
Martin
M
Reichert
Torsten E
TE
Wagner
Wilfried
W
Mueller-Klieser
Wolfgang
W
D000255:Adenosine Triphosphate / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002277:Carcinoma / Q000737:chemistry / Q000401:mortality / Q000601:surgery; D002294:Carcinoma, Squamous Cell; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005881:Gingiva / Q000737:chemistry*; D005947:Glucose / Q000032:analysis; D006019:Glycolysis; D006258:Head and Neck Neoplasms / Q000737:chemistry / Q000401:mortality / Q000601:surgery; D006801:Humans; D007633:Keratins / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D019344:Lactic Acid / Q000032:analysis; D049449:Luminescence; D008297:Male; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000737:chemistry / Q000401:mortality / Q000601:surgery; D011237:Predictive Value of Tests; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck
D014408:Biomarkers, Tumor; D019344:Lactic Acid; D007633:Keratins; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D005947:Glucose
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