期刊
MOLECULAR CANCER RESEARCH
卷 17, 期 4, 页码 949-962出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-18-0347
关键词
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资金
- Movember Foundation/Prostate Cancer Foundation of Australia [MRTA3, MRTA1]
- University of Sydney Robinson Fellowship
- Helen and Robert Ellis Postdoctoral Research Fellowship from the Sydney Medical School Foundation
- University of Sydney
- Sydney Medical School
- University of Sydney Australian Postgraduate Award
- National Health and Medical Research Council of Australia
- John Mills Young Investigator Award from the Prostate Cancer Foundation of Australia
- Principal Cancer Research Fellowship
- Cancer Council SA's Beat Cancer Project
- State Government of South Australia through the Department of Health
- Future Fellowship from the Australian Research Council [FT130101004]
- National Health and Medical Research Council [GNT1052963]
- Dutch Cancer Institute KWF
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 (similar to 83%) of carbons to the total lipid pool in all cell lines, compared with glucose (similar to 13%) and glutamine (similar to 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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