title: High glucose uptake unexpectedly is accompanied by high levels of the mitochondrial ß-F1-ATPase subunit in head and neck squamous cell carcinoma.
abstract: 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 (ß-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 ß-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 ß-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 ß-F1-ATPase to rapidly proliferate even in hypoxic zones, which are typical for HNSCC.
authors.affiliation: Jean-Uhrmacher-Institute for Otorhinolaryngological Research, University of Köln, 50924 Köln, Germany.
authors.forename: Christian U
authors.initials: CU
authors.lastname: Huebbers
authors.affiliation: Department of Pathology, Medical Faculty, University of Köln, 50924 Köln, Germany.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Adam
authors.affiliation: Department of Otolaryngology, Medical Faculty, University of Köln, 50924 Köln, Germany.
authors.forename: Simon F
authors.initials: SF
authors.lastname: Preuss
authors.affiliation: Center for Physiology and Pathophysiology, Institute of Vegetative Physiology, Medical Faculty, University of Köln, 50931 Köln, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Schiffer
authors.affiliation: Center for Physiology and Pathophysiology, Institute of Vegetative Physiology, Medical Faculty, University of Köln, 50931 Köln, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schilder
authors.affiliation: Department of Otorhinolaryngology, Jena University Hospital, 07740 Jena, Germany.
authors.forename: Orlando
authors.initials: O
authors.lastname: Guntinas-Lichius
authors.affiliation: Department of Nuclear Medicine, Medical Faculty, University of Köln, 50924 Köln, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University of Giessen, 35385 Giessen, Germany.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Klussmann
authors.affiliation: Center for Physiology and Pathophysiology, Institute of Vegetative Physiology, Medical Faculty, University of Köln, 50931 Köln, Germany.|Center for Molecular Medicine Cologne, CMMC, University of Köln, 50931 Köln, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Ageing-associated Diseases (CECAD), 50674 Köln, Germany.
authors.forename: Rudolf J
authors.initials: RJ
authors.lastname: Wiesner
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000032:analysis / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D019788:Fluorodeoxyglucose F18; D025261:Mitochondrial Proton-Translocating ATPases; D005947:Glucose
keywords: 18F-FDG-PET; HNSCC; OXPHOS; Warburg effect