Conditioned media from human pancreatic cancer cells reduces oleic acid oxidation in human myotubes

In the present study we wanted to metabolically compare healthy primary human pancreas epithelial cells (hPEC) to a pancreatic cancer cell line (PANC-1) and to explore the effect of exposing conditioned medium from the hPEC and PANC-1 cells on the energy metabolism in primary human myotubes. We studied differences in metabolism of glucose, oleic acid and lactic acid, as well as lactic acid production in the two pancreatic cell lines. Mass spectrometry-based proteomics was used to study global protein secretion from the two cell types and pathway analyses were performed. We observed that the PANC-1 cells did not exhibit a typical Warburg effect. Though they tended to have higher uptake of glucose and higher production of lactic acid, they also displayed a higher oxidation of glucose compared to hPEC cells. Interestingly, the PANC-1 cells had higher uptake but lower oxidation of oleic acid, and the mitochondrial reserve capacity from oleic acid was also lower in the PANC-1 cells. These changes in energy metabolism were reflected by differences in gene expressions, and differential expression of different pathways. Furthermore, conditioned media from the PANC-1 cells reduced the oleic acid oxidation in primary human skeletal muscle cells, but further studies will have to be conducted to reveal the mediator of this effect. Although this study is comparing a cancer cell line with a non-cancer cell line, we do not in any way imply that this represent cancer. This study merely represents the differences between the two different cell types studied.

本研究旨在从代谢维度比较健康原代人胰腺上皮细胞（healthy primary human pancreas epithelial cells, hPEC）与胰腺癌细胞系PANC-1，并探究原代人肌管暴露于hPEC与PANC-1细胞的条件培养基后，其能量代谢所受的影响。我们分析了两种胰腺细胞系在葡萄糖、油酸及乳酸代谢，以及乳酸生成方面的差异。本研究采用基于质谱的蛋白质组学（mass spectrometry-based proteomics）分析两种细胞的全局蛋白质分泌情况，并开展了通路分析。研究结果显示，PANC-1细胞并未表现出典型的沃伯格效应（Warburg effect）：尽管其葡萄糖摄取量与乳酸生成量均高于hPEC细胞，但葡萄糖氧化水平也更高。值得注意的是，PANC-1细胞对油酸的摄取量更高，但其油酸氧化水平却更低，且基于油酸的线粒体储备能力也弱于hPEC细胞。上述能量代谢变化可通过基因表达差异以及不同通路的差异化表达得到印证。此外，PANC-1细胞的条件培养基会抑制原代人骨骼肌细胞的油酸氧化，但我们仍需开展进一步研究以明确该效应的介导因子。尽管本研究将癌细胞系与非癌细胞系进行了比较，但我们绝非暗示该结果可代表癌症状态，本研究仅旨在阐明所研究的两种不同细胞类型之间的固有差异。