Winnike Jason H, Stewart Delisha A, Pathmasiri Wimal W, McRitchie Susan L, Sumner Susan J
Analytical Sciences, David H. Murdock Research Institute, Kannapolis, NC 28081, USA.
NIH Eastern Regional Comprehensive Metabolomics Resource Core, Department of Nutrition, University of North Carolina at Chapel Hill Nutrition Research Institute, Kannapolis, NC 28081, USA.
Int J Breast Cancer. 2018 Sep 30;2018:2063540. doi: 10.1155/2018/2063540. eCollection 2018.
To conduct an exploratory study to identify mechanisms that differentiate Luminal A (BT474 and MCF-7) and triple-negative (MDA-MB-231 and MDA-MB-468) breast cancer (BCa) cell lines to potentially provide novel therapeutic targets based on differences in energy utilization.
Cells were cultured in media containing either [U-C]-glucose or [U-C]-glutamine for 48 hours. Conditioned media and cellular extracts were analyzed by H and C NMR spectroscopy.
MCF-7 cells consumed the most glucose, producing the most lactate, demonstrating the greatest Warburg effect-associated energy utilization. BT474 cells had the highest tricarboxylic acid cycle (TCA) activity. The majority of energy utilization patterns in MCF-7 cells were more similar to MDA-MB-468 cells, while the patterns for BT474 cells were more similar to MDA-MB-231 cells. Compared to the Luminal A cell lines, TNBC cell lines consumed more glutamine and less glucose. BT474 and MDA-MB-468 cells produced high amounts of C-glycine from media [U-C]-glucose which was integrated into glutathione, indicating synthesis.
Stable isotopic resolved metabolomics using C substrates provided mechanistic information about energy utilization that was difficult to interpret using H data alone. Overall, cell lines that have different hormone receptor status have different energy utilization requirements, even if they are classified by the same clinical BCa subtype; and these differences offer clues about optimizing treatment strategies.
进行一项探索性研究，以确定区分 Luminal A 型（BT474 和 MCF-7）和三阴性（MDA-MB-231 和 MDA-MB-468）乳腺癌（BCa）细胞系的机制，从而有可能基于能量利用差异提供新的治疗靶点。
将细胞在含有[U-¹³C]-葡萄糖或[U-¹³C]-谷氨酰胺的培养基中培养48小时。通过¹H和¹³C核磁共振波谱分析条件培养基和细胞提取物。
MCF-7 细胞消耗的葡萄糖最多，产生的乳酸最多，显示出与瓦伯格效应相关的最大能量利用。BT474 细胞具有最高的三羧酸循环（TCA）活性。MCF-7 细胞中的大多数能量利用模式与 MDA-MB-468 细胞更相似，而 BT474 细胞的模式与 MDA-MB-231 细胞更相似。与 Luminal A 型细胞系相比，三阴性乳腺癌细胞系消耗更多的谷氨酰胺和更少的葡萄糖。BT474 和 MDA-MB-468 细胞从培养基[U-¹³C]-葡萄糖中产生大量的¹³C-甘氨酸，这些甘氨酸整合到谷胱甘肽中，表明有合成过程。
使用¹³C底物的稳定同位素分辨代谢组学提供了有关能量利用的机制信息，仅使用¹H数据难以解释这些信息。总体而言，具有不同激素受体状态的细胞系具有不同的能量利用需求，即使它们按相同的临床 BCa 亚型分类；这些差异为优化治疗策略提供了线索。
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