Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Norway.
Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Norway.
Pancreatology. 2020 Jun;20(4):676-682. doi: 10.1016/j.pan.2020.04.014. Epub 2020 Apr 22.
/Objectives: We aimed to metabolically compare healthy primary human pancreatic epithelial cells (hPEC) to a pancreatic cancer cell line (PANC-1) and explore the effect on energy metabolism of exposing primary human myotubes to conditioned medium from hPEC and PANC-1 cells.
Differences in metabolism were examined with radiolabeled glucose, oleic acid and lactic acid, and by qPCR. Mass spectrometry-based proteomics was used to study global protein secretion from the two cell types. Pathway analyses were performed.
PANC-1 cells tended to have higher glucose uptake, production of lactic acid, and glucose oxidation compared to hPEC cells. PANC-1 cells had higher uptake but lower oxidation of oleic acid, and mitochondrial reserve capacity from oleic acid was lower in PANC-1 cells. These differences in energy metabolism were reflected by differences in gene expressions and pathway analyses of the secretome. Conditioned medium from PANC-1 cells attenuated oleic acid oxidation in primary human myotubes.
Metabolic characterization of the PANC-1 cells revealed a glycolytic phenotype since they had an active glucose oxidation. Furthermore, PANC-1 cells showed a lower oleic acid oxidation and secreted a high amount of proteins into conditioned medium that also induced a reduced oleic acid oxidation in myotubes.
/目的:我们旨在对健康的原代人胰腺上皮细胞(hPEC)与胰腺癌细胞系(PANC-1)进行代谢比较,并研究将 hPEC 和 PANC-1 细胞的条件培养基暴露于人原代肌管对能量代谢的影响。
使用放射性标记的葡萄糖、油酸和乳酸以及 qPCR 检查代谢差异。基于质谱的蛋白质组学用于研究两种细胞类型的全局蛋白质分泌。进行了途径分析。
与 hPEC 细胞相比,PANC-1 细胞的葡萄糖摄取、乳酸生成和葡萄糖氧化作用往往更高。PANC-1 细胞对油酸的摄取较高,但氧化较低,且来自油酸的线粒体储备能力在 PANC-1 细胞中较低。这些能量代谢差异反映在分泌组的基因表达和途径分析中。来自 PANC-1 细胞的条件培养基减弱了原代人肌管中油酸的氧化。
PANC-1 细胞的代谢特征表明其具有活跃的葡萄糖氧化作用,表现出糖酵解表型。此外,PANC-1 细胞的油酸氧化较低,并分泌大量蛋白质进入条件培养基,这也导致肌管中的油酸氧化减少。