Kim Francis Andersen1, Vadim Divilov2, Kuntalkumar Sevak2, Jacek Koziorowski3, Jason S Lewis2, NagaVarakishore Pillarsetty2. 1. Department of Clinical Physiology & Nuclear Medicine, Herlev Hospital, University Hospital of Copenhagen, Herlev, Denmark. Electronic address: dr.kimfandersen@hotmail.com. 2. Radiochemistry & Imaging Sciences Services, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. 3. Department of Clinical Physiology & Nuclear Medicine, Herlev Hospital, University Hospital of Copenhagen, Herlev, Denmark.
Abstract
INTRODUCTION: The study focuses on the interaction between glucose and free fatty acids (FFA) in malignant human prostate cancer cell lines by an in vitro observation of uptake of fluoro-2-deoxy-D-glucose (FDG) and acetate. METHODS: Human prostate cancer cell lines (PC3, CWR22Rv1, LNCaP, and DU145) were incubated for 2 h and 24 h in glucose-containing (5.5 mM) Dulbecco's Modified Eagle's Medium (DMEM) with varying concentrations of the free fatty acid palmitate (0-1.0 mM). Then the cells were incubated with [(18)F]-FDG (1 μCi/mL; 0.037 MBq/mL) in DMEM either in presence or absence of glucose and in presence of varying concentrations of palmitate for 1 h. Standardized procedures regarding cell counting and measuring for (18)F radioactivity were applied. Cell uptake studies with (14)C-1-acetate under the same conditions were performed on PC3 cells. RESULTS: In glucose containing media there was significantly increased FDG uptake after 24 h incubation in all cell lines, except DU145, when upper physiological levels of palmitate were added. A 4-fold increase of FDG uptake in PC3 cells (15.11% vs. 3.94%/10(6) cells) was observed in media with 1.0 mM palmitate compared to media with no palmitate. The same tendency was observed in PC3 and CWR22Rv1 cells after 2 h incubation. In glucose-free media no significant differences in FDG uptake after 24 h incubation were observed. The significant differences after 2 h incubation all pointed in the direction of increased FDG uptake when palmitate was added. Acetate uptake in PC3 cells was significantly lower when palmitate was added in glucose-free DMEM. No clear tendency when comparing FDG or acetate uptake in the same media at different time points of incubation was observed. CONCLUSIONS: Our results indicate a FFA dependent metabolic boost/switch of glucose uptake in PCa, with patterns reflecting the true heterogeneity of the disease.
INTRODUCTION: The study focuses on the interaction between glucose and free fatty acids (FFA) in malignant humanprostate cancer cell lines by an in vitro observation of uptake of fluoro-2-deoxy-D-glucose (FDG) and acetate. METHODS:Humanprostate cancer cell lines (PC3, CWR22Rv1, LNCaP, and DU145) were incubated for 2 h and 24 h in glucose-containing (5.5 mM) Dulbecco's Modified Eagle's Medium (DMEM) with varying concentrations of the free fatty acidpalmitate (0-1.0 mM). Then the cells were incubated with [(18)F]-FDG (1 μCi/mL; 0.037 MBq/mL) in DMEM either in presence or absence of glucose and in presence of varying concentrations of palmitate for 1 h. Standardized procedures regarding cell counting and measuring for (18)F radioactivity were applied. Cell uptake studies with (14)C-1-acetate under the same conditions were performed on PC3 cells. RESULTS: In glucose containing media there was significantly increased FDG uptake after 24 h incubation in all cell lines, except DU145, when upper physiological levels of palmitate were added. A 4-fold increase of FDG uptake in PC3 cells (15.11% vs. 3.94%/10(6) cells) was observed in media with 1.0 mM palmitate compared to media with no palmitate. The same tendency was observed in PC3 and CWR22Rv1 cells after 2 h incubation. In glucose-free media no significant differences in FDG uptake after 24 h incubation were observed. The significant differences after 2 h incubation all pointed in the direction of increased FDG uptake when palmitate was added. Acetate uptake in PC3 cells was significantly lower when palmitate was added in glucose-free DMEM. No clear tendency when comparing FDG or acetate uptake in the same media at different time points of incubation was observed. CONCLUSIONS: Our results indicate a FFA dependent metabolic boost/switch of glucose uptake in PCa, with patterns reflecting the true heterogeneity of the disease.
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