Wojtowicz Wojciech, Wróbel Anna, Pyziak Karolina, Tarkowski Radosław, Balcerzak Alicja, Bębenek Marek, Młynarz Piotr
Department of Biochemistry, Biotechnology and Molecular Biology, Bioanalytical Laboratory, Wroclaw University of Science and Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland.
Ryvu Therapeutics S.A., Bobrzynskiego 14; 30-348 Krakow, Poland.
Metabolites. 2020 Apr 27;10(5):173. doi: 10.3390/metabo10050173.
Triple-negative breast cancer (TNBC) is characterized by limited survival, poor prognosis, and high recurrence. Understanding the metabolic adaptations of TNBC could help reveal improved treatment regiments. Here we performed a comprehensive H NMR metabolic characterization of the MDA-MB-468 cell line, a commonly used model of TNBC, followed by an analysis of serum samples obtained from TNBC patients and healthy controls. MDA-MB-468 cells were cultured, and changes in the metabolic composition of the medium were monitored for 72 h. Based on time courses, metabolites were categorized as being consumed, being produced, or showing a mixed behavior. When comparing TNBC and control samples (HC), and by using multivariate and univariate analyses, we identified nine metabolites with differing profiles). The serum of TNBC patients was characterized by higher levels of glucose, glutamine, citrate, and acetoacetate and by lower levels of lactate, alanine, tyrosine, glutamate, and acetone. A comparative analysis between MDA-MB-468 cell culture media and TNBC patients' serum identified a potential systemic response to the carcinogenesis-associated processes, highlighting that MDA-MB-468 cells footprint does not reflect metabolic changes observed in studied TNBC serum fingerprint.
三阴性乳腺癌（TNBC）的特征是生存期有限、预后不良和高复发率。了解TNBC的代谢适应性有助于揭示改进的治疗方案。在此，我们对MDA-MB-468细胞系（一种常用的TNBC模型）进行了全面的核磁共振氢谱代谢特征分析，随后分析了TNBC患者和健康对照者的血清样本。培养MDA-MB-468细胞，并监测培养基代谢成分72小时的变化。根据时间进程，将代谢物分为消耗型、产生型或表现出混合行为型。在比较TNBC和对照样本（HC）时，通过多变量和单变量分析，我们鉴定出九种具有不同谱型的代谢物。TNBC患者血清的特征是葡萄糖、谷氨酰胺、柠檬酸盐和乙酰乙酸水平较高，而乳酸、丙氨酸、酪氨酸、谷氨酸和丙酮水平较低。MDA-MB-468细胞培养基与TNBC患者血清之间的比较分析确定了对致癌相关过程的潜在全身反应，突出表明MDA-MB-468细胞特征并不反映在研究的TNBC血清指纹中观察到的代谢变化。
