Stable Isotope-Resolved Metabolomic Differences between Hormone-Responsive and Triple-Negative Breast Cancer Cell Lines.

IF 1.6 Q4 ONCOLOGY International Journal of Breast Cancer Pub Date : 2018-09-30 eCollection Date: 2018-01-01 DOI:10.1155/2018/2063540
Jason H Winnike, Delisha A Stewart, Wimal W Pathmasiri, Susan L McRitchie, Susan J Sumner
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引用次数: 17

Abstract

Purpose: 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.

Methods: Cells were cultured in media containing either [U-13C]-glucose or [U-13C]-glutamine for 48 hours. Conditioned media and cellular extracts were analyzed by 1H and 13C NMR spectroscopy.

Results: 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 13C-glycine from media [U-13C]-glucose which was integrated into glutathione, indicating de novo synthesis.

Conclusions: Stable isotopic resolved metabolomics using 13C substrates provided mechanistic information about energy utilization that was difficult to interpret using 1H 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.

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激素反应性和三阴性乳腺癌细胞系稳定同位素分解代谢组学差异
目的:开展一项探索性研究,以确定区分Luminal A (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,以潜在地提供基于能量利用差异的新治疗靶点。方法: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。用1H和13C NMR对条件培养基和细胞提取物进行分析。结果:MCF-7细胞消耗最多的葡萄糖,产生最多的乳酸,显示出最大的Warburg效应相关的能量利用。BT474细胞三羧酸循环(TCA)活性最高。MCF-7细胞的大部分能量利用模式更类似于MDA-MB-468细胞,而BT474细胞的模式更类似于MDA-MB-231细胞。与Luminal A细胞系相比,TNBC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]-葡萄糖中产生了大量的13c -甘氨酸,这些13c -甘氨酸被整合到谷胱甘肽中,表明是从头合成的。结论:使用13C底物的稳定同位素分解代谢组学提供了难以单独使用1H数据解释的能量利用的机制信息。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,即使它们被相同的临床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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来源期刊
CiteScore
3.40
自引率
0.00%
发文量
25
审稿时长
19 weeks
期刊介绍: International Journal of Breast Cancer is a peer-reviewed, Open Access journal that provides a forum for scientists, clinicians, and health care professionals working in breast cancer research and management. The journal publishes original research articles, review articles, and clinical studies related to molecular pathology, genomics, genetic predisposition, screening and diagnosis, disease markers, drug sensitivity and resistance, as well as novel therapies, with a specific focus on molecular targeted agents and immune therapies.
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