Differential Utilization of Dietary Fatty Acids in Benign and Malignant Cells of the Prostate.
Tumor cells adapt via metabolic reprogramming to meet elevated energy demands due to continuous proliferation, for example by switching to alternative energy sources. Nutrients such as glucose, fatty acids, ketone bodies and amino acids may be utilized as preferred substrates to fulfill increased energy requirements. In this study we investigated the metabolic characteristics of benign and cancer cells of the prostate with respect to their utilization of medium chain (MCTs) and long chain triglycerides (LCTs) under standard and glucose-starved culture conditions by assessing cell viability, glycolytic activity, mitochondrial respiration, the expression of genes encoding key metabolic enzymes as well as mitochondrial mass and mtDNA content. We report that BE prostate cells (RWPE-1) have a higher competence to utilize fatty acids as energy source than PCa cells (LNCaP, ABL, PC3) as shown not only by increased cell viability upon fatty acid supplementation but also by an increased ß-oxidation of fatty acids, although the base-line respiration was 2-fold higher in prostate cancer cells. Moreover, BE RWPE-1 cells were found to compensate for glucose starvation in the presence of fatty acids. Of notice, these findings were confirmed in vivo by showing that PCa tissue has a lower capacity in oxidizing fatty acids than benign prostate. Collectively, these metabolic differences between benign and prostate cancer cells and especially their differential utilization of fatty acids could be exploited to establish novel diagnostic and therapeutic strategies.
Division of Experimental Urology, Department of Urology, Medical University of Innsbruck, Innsbruck, Austria; Oncotyrol GmbH, Center for Personalized Medicine, Innsbruck, Austria.
Andrea
A
Dueregger
Oncotyrol GmbH, Center for Personalized Medicine, Innsbruck, Austria; Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria; Oroboros Instruments, High-Resolution Respirometry, Innsbruck, Austria.
Bernd
B
Schöpf
Division of Experimental Urology, Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.
Theresa
T
Eder
Division of Experimental Urology, Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.
Julia
J
Höfer
Oroboros Instruments, High-Resolution Respirometry, Innsbruck, Austria; Department of General and Transplant Surgery, D. Swarovski Research Laboratory, Medical University of Innsbruck, Innrain 66/6, A-6020, Innsbruck, Austria.
Erich
E
Gnaiger
Clinical Institute for Pathology, Medical University Vienna, Vienna, Austria.
Astrid
A
Aufinger
Clinical Institute for Pathology, Medical University Vienna, Vienna, Austria.
Lukas
L
Kenner
Diätologie, FHG-Zentrum Für Gesundheitsberufe Tirol GmbH, Innsbruck, Austria.
Bernhard
B
Perktold
Diätologie, FHG-Zentrum Für Gesundheitsberufe Tirol GmbH, Innsbruck, Austria.
Reinhold
R
Ramoner
Division of Experimental Urology, Department of Urology, Medical University of Innsbruck, Innsbruck, Austria; Oncotyrol GmbH, Center for Personalized Medicine, Innsbruck, Austria.
Helmut
H
Klocker
Division of Experimental Urology, Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.
Iris E
IE
Eder
D000368:Aged; D045744:Cell Line, Tumor; D019069:Cell Respiration; D002470:Cell Survival; D004272:DNA, Mitochondrial / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D018628:Gene Dosage; D054629:Genome, Mitochondrial / Q000235:genetics; D006019:Glycolysis; D006801:Humans; D007657:Ketone Bodies / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D053142:Mitochondrial Size; D010085:Oxidative Phosphorylation; D011467:Prostate / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D014280:Triglycerides / Q000378:metabolism
D004272:DNA, Mitochondrial; D004041:Dietary Fats; D005227:Fatty Acids; D007657:Ketone Bodies; D014280:Triglycerides