Metabolic characterization of invaded cells of the pancreatic cancer cell line, PANC-1.
Metabolic characterization of invaded cells of the pancreatic cancer cell line, PANC-1.
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DOI：
10.1111/cas.13220
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发表时间：
2017-05
期刊：
影响因子：
5.7
通讯作者：
Imai T
中科院分区：
文献类型：
--
作者：
Fujita M;Imadome K;Imai T
我们之前报道，在transwell侵袭实验中，培养的人胰腺癌细胞系PANC‐1中约有0.4%的细胞可以入侵基质，这表明这些入侵的PANC‐1细胞可能具有特定的特征以保持其侵袭潜力。为了确定入侵PANC‐1细胞的代谢特征，使用CE‐TOFMS对入侵PANC‐1细胞与整个培养PANC‐1细胞进行了代谢组分析，并测量了110种代谢物的浓度。与整个培养细胞相比，入侵的PANC‐1的特征是氨基酸和TCA循环中间体水平降低，糖酵解和核酸代谢中间体水平降低或增加。特别是，在入侵细胞中，腺苷和鸟苷的能量电荷比例都降低了，这表明在入侵细胞中ATP和GTP的消耗很高，从而表明ATP或GTP的产生途径受到刺激。此外，侵染细胞的GSH/GSSG比例较低，但过氧化氢处理后细胞的存活比例较高。因此，入侵细胞是抗氧化应激的群体。此外，细胞内GSH含量的降低抑制了PANC‐1的侵袭性，表明GSH在PANC‐1的侵袭性中起重要作用。总的来说，我们认为被入侵的细胞有几个独特的代谢特征。
We previously reported that about 0.4% of cells in the cultured human pancreatic cancer cell line, PANC‐1, can invade matrigel during the transwell invasion assay, suggesting that these invaded PANC‐1 cells may have specific characteristics to keep their invasive potential. To identify the metabolic characterization specific in the invaded PANC‐1 cells, metabolome analysis of the invaded PANC‐1 compared with the whole cultured PANC‐1 was performed using CE‐TOFMS, and concentrations of 110 metabolites were measured. In contrast to the whole cultured cells, the invaded PANC‐1 was characterized as a population with reduced levels of amino acids and TCA cycle intermediates, and decreased and increased intermediates in glycolysis and nucleic acid metabolism. In particular, the ratio of both adenosine and guanosine energy charge was reduced in the invaded cells, revealing that the consumption of ATP and GTP was high in the invaded cells, and thus suggesting that ATP‐ or GTP‐generating pathways are stimulated. In addition, the GSH/GSSG ratio was low in the invaded cells, but these cells had a higher surviving fraction after exposure to hydrogen peroxide. Thus, the invaded cells were the population resistant to oxidative stress. Furthermore, reduction in intracellular GSH content inhibited PANC‐1 invasiveness, indicated that GSH has an important role in PANC‐1 invasiveness. Overall, we propose the invaded cells have several unique metabolic profiles.