Willmann Lucas, Erbes Thalia, Halbach Sebastian, Brummer Tilman, Jäger Markus, Hirschfeld Marc, Fehm Tanja, Neubauer Hans, Stickeler Elmar, Kammerer Bernd
Center for Biological Systems Analysis ZBSA, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.
Institute of Biology II, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.
Sci Rep. 2015 Aug 21;5:13374. doi: 10.1038/srep13374.
Cancer cells show characteristic effects on cellular turnover and DNA/RNA modifications leading to elevated levels of excreted modified nucleosides. We investigated the molecular signature of different subtypes of breast cancer cell lines and the breast epithelial cell line MCF-10A. Prepurification of cell culture supernatants was performed by cis-diol specific affinity chromatography using boronate-derivatized polyacrylamide gel. Samples were analyzed by application of reversed phase chromatography coupled to a triple quadrupole mass spectrometer. Collectively, we determined 23 compounds from RNA metabolism, two from purine metabolism, five from polyamine/methionine cycle, one from histidine metabolism and two from nicotinate and nicotinamide metabolism. We observed major differences of metabolite excretion pattern between the breast cancer cell lines and MCF-10A, just as well as between the different breast cancer cell lines themselves. Differences in metabolite excretion resulting from cancerous metabolism can be integrated into altered processes on the cellular level. Modified nucleosides have great potential as biomarkers in due consideration of the heterogeneity of breast cancer that is reflected by the different molecular subtypes of breast cancer. Our data suggests that the metabolic signature of breast cancer cell lines might be a more subtype-specific tool to predict breast cancer, rather than a universal approach.
癌细胞对细胞更新以及DNA/RNA修饰具有特征性影响,导致排泄的修饰核苷水平升高。我们研究了乳腺癌细胞系不同亚型以及乳腺上皮细胞系MCF-10A的分子特征。通过使用硼酸酯衍生的聚丙烯酰胺凝胶的顺二醇特异性亲和色谱法对细胞培养上清液进行预纯化。通过将反相色谱与三重四极杆质谱仪联用对样品进行分析。我们总共确定了来自RNA代谢的23种化合物、来自嘌呤代谢的2种化合物、来自多胺/甲硫氨酸循环的5种化合物、来自组氨酸代谢的1种化合物以及来自烟酸和烟酰胺代谢的2种化合物。我们观察到乳腺癌细胞系与MCF-10A之间以及不同乳腺癌细胞系自身之间代谢物排泄模式存在主要差异。由癌性代谢导致的代谢物排泄差异可整合到细胞水平的改变过程中。考虑到乳腺癌不同分子亚型所反映的乳腺癌异质性,修饰核苷作为生物标志物具有巨大潜力。我们的数据表明,乳腺癌细胞系的代谢特征可能是预测乳腺癌的更具亚型特异性的工具,而非通用方法。