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: Christian U Huebbers, Alexander C Adam, Simon F Preuss, Theresa Schiffer, Sarah Schilder, Orlando Guntinas-Lichius, Matthias Schmidt, Jens P Klussmann, Rudolf J Wiesner
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 34 Pg. 36172-84 (Nov 03 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 26452026 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fluorodeoxyglucose F18
• Mitochondrial Proton-Translocating ATPases
• Glucose

Topics

• Carcinoma, Squamous Cell (diagnostic imaging, enzymology, metabolism)
• Female
• Fluorodeoxyglucose F18 (analysis, pharmacokinetics)
• Glucose (metabolism)
• Head and Neck Neoplasms (diagnostic imaging, enzymology, metabolism)
• Humans
• Male
• Middle Aged
• Mitochondria (enzymology, metabolism)
• Mitochondrial Proton-Translocating ATPases (metabolism)
• Positron-Emission Tomography (methods)
• Squamous Cell Carcinoma of Head and Neck