Willmann Lucas, Schlimpert Manuel, Halbach Sebastian, Erbes Thalia, 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.
Center for Biological Systems Analysis ZBSA, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.
J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Sep 1;1000:95-104. doi: 10.1016/j.jchromb.2015.07.021. Epub 2015 Jul 14.
Although the concept of aerobic glycolysis in cancer was already reported in the 1930s by Otto Warburg, the understanding of metabolic pathways remains challenging especially due to the heterogeneity of cancer. In consideration of four different time points (1, 2, 4, and 7 days of incubation), GC-MS profiling of metabolites was performed on cell extracts and supernatants of breast cancer cell lines (MDA-MB-231, -453, BT-474) with different sub classification and the breast epithelial cell line MCF-10A. To the exclusion of trypsinization, direct methanolic extraction, cell scraping and cell disruption was executed to obtain central metabolites. Major differences in biochemical pathways have been observed in the breast cancer cell lines compared to the breast epithelial cell line, as well as between the breast cancer cell lines themselves. Characteristics of breast cancer subtypes could be correlated to their individual metabolic profiles. PLS-DA revealed the discrimination of breast cancer cell lines from MCF-10A based on elevated amino acid levels. The observed metabolic signatures have great potential as biomarker for breast cancer as well as an improved understanding of subtype specific phenomenons of breast cancer.
尽管奥托·瓦尔堡在20世纪30年代就已报道了癌症中需氧糖酵解的概念，但对代谢途径的理解仍然具有挑战性，尤其是由于癌症的异质性。考虑到四个不同的时间点（培养1、2、4和7天），对具有不同亚分类的乳腺癌细胞系（MDA-MB-231、-453、BT-474）和乳腺上皮细胞系MCF-10A的细胞提取物和上清液进行了代谢物的气相色谱-质谱分析。为避免胰蛋白酶消化，采用直接甲醇提取、细胞刮擦和细胞破碎的方法来获取中心代谢物。与乳腺上皮细胞系相比，在乳腺癌细胞系之间以及乳腺癌细胞系自身之间均观察到生化途径的主要差异。乳腺癌亚型的特征可能与其各自的代谢谱相关。偏最小二乘判别分析（PLS-DA）显示，基于氨基酸水平升高可区分乳腺癌细胞系与MCF-10A。观察到的代谢特征作为乳腺癌的生物标志物以及对乳腺癌亚型特异性现象的更好理解具有巨大潜力。
