High glucose uptake unexpectedly is accompanied by high levels of the mitochondrial β-F1-ATPase subunit in head and neck squamous cell carcinoma
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Christian U. Huebbers1,*, Alexander C. Adam2,*, Simon F. Preuss3, Theresa Schiffer4, Sarah Schilder4, Orlando Guntinas-Lichius5, Matthias Schmidt6, Jens P. Klussmann7, Rudolf J. Wiesner4,8,9
1Jean-Uhrmacher-Institute for Otorhinolaryngological Research, University of Köln, 50924 Köln, Germany
2Department of Pathology, Medical Faculty, University of Köln, 50924 Köln, Germany
3Department of Otolaryngology, Medical Faculty, University of Köln, 50924 Köln, Germany
4Center for Physiology and Pathophysiology, Institute of Vegetative Physiology, Medical Faculty, University of Köln, 50931 Köln, Germany
5Department of Otorhinolaryngology, Jena University Hospital, 07740 Jena, Germany
6Department of Nuclear Medicine, Medical Faculty, University of Köln, 50924 Köln, Germany
7Department of Otorhinolaryngology, Head and Neck Surgery, University of Giessen, 35385 Giessen, Germany
8Center for Molecular Medicine Cologne, CMMC, University of Köln, 50931 Köln, Germany
9Cologne Excellence Cluster on Cellular Stress Responses in Ageing-associated Diseases (CECAD), 50674 Köln, Germany
*These authors have contributed equally to this work
Rudolf J. Wiesner, e-mail: [email protected]
Keywords: HNSCC, OXPHOS, 18F-FDG-PET, Warburg effect
Received: March 09, 2015 Accepted: September 24, 2015 Published: October 06, 2015
A hallmark of solid tumors is the consumption of large amounts of glucose and production of lactate, also known as Warburg-like metabolism. This metabolic phenotype is typical for aggressive tumor growth, and can be visualized by 18F-fluorodeoxyglucose (18F-FDG) uptake detected by positron emission tomography (PET). High 18F-FDG uptake inversely correlates with survival and goes along with reduced expression of the catalytic beta-subunit of the H+-ATP synthase (β-F1-ATPase) in several tumor entities analyzed so far.
For this study we characterized a series of 15 head and neck squamous cell carcinoma (HNSCC) by (i) determining 18F-FDG-uptake; (ii) quantitative expression analysis of β-F1-ATPase (Complex V), NDUF-S1 (Complex I) and COX1 (Complex IV) of the mitochondrial electron transport chain (ETC), as well as Hsp60 (mitochondrial mass) and GAPDH (glycolysis) in tumor cells; (iii) sequencing of the mtDNA of representative tumor samples.
Whereas high 18F-FDG-uptake also correlates with poor prognosis in HNSCC, it surprisingly is accompanied by high levels of β-F1-ATPase, but not by any of the other analyzed proteins.
In conclusion, we here describe a completely new phenotype of metabolic adaptation possibly enabling those tumors with highest levels of β-F1-ATPase to rapidly proliferate even in hypoxic zones, which are typical for HNSCC.
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