11C‐acetate positron‐emission tomography/computed tomography imaging for detection of recurrent disease after radical prostatectomy or radiotherapy in patients with prostate cancer

Esch, Lukas; Fahlbusch, M.; Albers, Peter; Hautzel, Hubertus; Müller-Mattheis, V.

doi:10.1111/bju.13706

Cited by 4 publications

(1 citation statement)

References 25 publications

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“…While the functional significance of these phenotypes is yet to be elucidated, they likely arise from aberrant activation of SREBPs and enhanced expression of FASN (14)(15)(16). The resultant increase in de novo FA synthesis, which uses acetyl-CoA as a major substrate, is the basis for evaluating 11 C-acetate-PET for diagnosis and staging (17); however, the influence of factors other than tumor metabolism on acetate uptake results in high false-positive results (17). One potential driving factor that influences 11 Cacetate uptake and metabolism could be the extratumoral lipid environment.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Fatty Acids Are the Major Contributor to Lipid Synthesis in Prostate Cancer

Balaban

Nassar

Zhang

et al. 2019

Molecular Cancer Research

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Prostate cancer cells exhibit altered cellular metabolism but, notably, not the hallmarks of Warburg metabolism. Prostate cancer cells exhibit increased de novo synthesis of fatty acids (FA); however, little is known about how extracellular FAs, such as those in the circulation, may support prostate cancer progression. Here, we show that increasing FA availability increased intracellular triacylglycerol content in cultured patient-derived tumor explants, LNCaP and C4-2B spheroids, a range of prostate cancer cells (LNCaP, C4-2B, 22Rv1, PC-3), and prostate epithelial cells (PNT1). Extracellular FAs are the major source ($83%) of carbons to the total lipid pool in all cell lines, compared with glucose ($13%) and glutamine ($4%), and FA oxidation rates are greater in prostate cancer cells compared with PNT1 cells, which preferentially partitioned extracellular FAs into triacylglycerols. Because of the higher rates of FA oxidation in C4-2B cells, cells remained viable when challenged by the addition of palmitate to culture media and inhibition of mitochondrial FA oxidation sensitized C4-2B cells to palmitate-induced apoptosis. Whereas in PC-3 cells, palmitate induced apoptosis, which was prevented by pretreatment of PC-3 cells with FAs, and this protective effect required DGAT-1-mediated triacylglycerol synthesis. These outcomes highlight for the first-time heterogeneity of lipid metabolism in prostate cancer cells and the potential influence that obesity-associated dyslipidemia or host circulating has on prostate cancer progression.Implications: Extracellular-derived FAs are primary building blocks for complex lipids and heterogeneity in FA metabolism exists in prostate cancer that can influence tumor cell behavior.

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