Hutschenreuther Antje, Birkenmeier Gerd, Bigl Marina, Krohn Knut, Birkemeyer Claudia
Medical Faculty, Institute of Biochemistry, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany.
University of Leipzig, IZKF Core Unit DNA-Technologies, Liebigstr 21, 04103 Leipzig, Germany.
Metabolites. 2013 Nov 27;3(4):1084-101. doi: 10.3390/metabo3041084.
In cancer research, cell lines are used to explore the molecular basis of the disease as a substitute to tissue biopsies. Breast cancer in particular is a very heterogeneous type of cancer, and different subgroups of cell lines have been established according to their genomic profiles and tumor characteristics. We applied GCMS metabolite profiling to five selected breast cancer cell lines and found this heterogeneity reflected on the metabolite level as well. Metabolite profiles of MCF-7 cells belonging to the luminal gene cluster proved to be more different from those of the basal A cell line JIMT-1 and the basal B cell lines MDA-MB-231, MDA-MB-435, and MDA-MB-436 with only slight differences in the intracellular metabolite pattern. Lactate release into the cultivation medium as an indicator of glycolytic activity was correlated to the metabolite profiles and physiological characteristics of each cell line. In conclusion, pantothenic acid, beta-alanine and glycerophosphoglycerol appeared to be related to the glycolytic activity designated through high lactate release. Other physiological parameters coinciding with glycolytic activity were high glyoxalase 1 (Glo1) and lactate dehydrogenase (LDH) enzyme activity as well as cell migration as an additional important characteristic contributing to the aggressiveness of tumor cells. Metabolite profiles of the cell lines are comparatively discussed with respect to known biomarkers of cancer progression.
在癌症研究中,细胞系被用作探索疾病分子基础的工具,以替代组织活检。尤其是乳腺癌,它是一种非常异质性的癌症类型,已根据其基因组图谱和肿瘤特征建立了不同的细胞系亚群。我们对五个选定的乳腺癌细胞系进行了气相色谱 - 质谱代谢物谱分析,发现这种异质性在代谢物水平上也有所体现。属于管腔基因簇的MCF - 7细胞的代谢物谱与基底A细胞系JIMT - 1以及基底B细胞系MDA - MB - 231、MDA - MB - 435和MDA - MB - 436的代谢物谱差异更大,而细胞内代谢物模式只有轻微差异。作为糖酵解活性指标的乳酸释放到培养基中与每个细胞系的代谢物谱和生理特征相关。总之,泛酸、β - 丙氨酸和甘油磷酸甘油似乎与通过高乳酸释放所表明的糖酵解活性有关。与糖酵解活性一致的其他生理参数包括高乙二醛酶1(Glo1)和乳酸脱氢酶(LDH)酶活性,以及细胞迁移,细胞迁移是导致肿瘤细胞侵袭性的另一个重要特征。本文还针对已知的癌症进展生物标志物对细胞系的代谢物谱进行了比较讨论。