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Targeted metabolomics reveals dynamic portrayal of amino acids and derivatives in triple-negative breast cancer cells and culture media
Molecular Omics ( IF 2.9 ) Pub Date : 2020-11-23 , DOI: 10.1039/d0mo00126k Fang Kou 1 , Bangjie Zhu , Wenbin Zhou , Chunming Lv , Yu Cheng , Hai Wei
Molecular Omics ( IF 2.9 ) Pub Date : 2020-11-23 , DOI: 10.1039/d0mo00126k Fang Kou 1 , Bangjie Zhu , Wenbin Zhou , Chunming Lv , Yu Cheng , Hai Wei
Affiliation
Triple-negative breast cancer (TNBC) is well-known for its metastatic aggressiveness and poor survival prognosis, accounting for nearly a quarter of cases in breast cancer. We performed intra- and extra-cellular profiling of 40 amino acids and derivatives on three cell lines and their culture media, including TNBC, non-TNBC and normal breast epithelial cells, using HILIC-MS/MS. Characteristic metabolic alteration of amino acids and derivatives was observed in TNBC cells, compared to non-TNBC cells, especially in correlated intra- and extra-cellular metabolic pathways. Intra-cellularly, quantified glutamic acid, β-alanine, aspartic acid, glutathione, N-acetyl-serine and N-acetyl-methionine were most significantly increased (>2-fold, p < 0.01 and VIP > 1) in TNBC cells. Extra-cellularly, significantly increased uptake of glutamine, serine, β-alanine, and lysine and elevated excretion of glutamic acid and L-cysteine-glutathione (p < 0.01 and VIP > 1) were observed by TNBC cells from or to their cell culture media. This study depicted a novel dynamic portrayal of metabolic dysregulation between TNBC and non-TNBC cells, correlated in both intra- and extra-cellular amino acid profiles. Quantification of these distinctive metabolites of TNBC cells might offer advanced understanding and new treatment targets for TNBC.
中文翻译:
靶向代谢组学揭示了三阴性乳腺癌细胞和培养基中氨基酸和衍生物的动态描绘
三阴性乳腺癌 (TNBC) 以其转移侵袭性和较差的生存预后而闻名,占乳腺癌病例的近四分之一。我们使用 HILIC-MS/MS 对三种细胞系及其培养基(包括 TNBC、非 TNBC 和正常乳腺上皮细胞)进行了 40 种氨基酸和衍生物的细胞内和细胞外分析。与非 TNBC 细胞相比,在 TNBC 细胞中观察到氨基酸和衍生物的特征性代谢改变,尤其是在相关的细胞内和细胞外代谢途径中。在细胞内,定量的谷氨酸、β-丙氨酸、天冬氨酸、谷胱甘肽、N-乙酰-丝氨酸和N-乙酰-甲硫氨酸增加最显着(>2 倍,p< 0.01 和 VIP > 1) 在 TNBC 细胞中。在细胞外,TNBC 细胞从细胞培养物中观察到谷氨酰胺、丝氨酸、β-丙氨酸和赖氨酸的摄取显着增加,谷氨酸和L-半胱氨酸-谷胱甘肽的排泄增加(p < 0.01 和 VIP > 1)媒体。这项研究描绘了 TNBC 和非 TNBC 细胞之间代谢失调的新动态描述,与细胞内和细胞外氨基酸谱相关。TNBC 细胞的这些独特代谢物的定量可能为 TNBC 提供先进的理解和新的治疗目标。
更新日期:2020-12-09
中文翻译:
靶向代谢组学揭示了三阴性乳腺癌细胞和培养基中氨基酸和衍生物的动态描绘
三阴性乳腺癌 (TNBC) 以其转移侵袭性和较差的生存预后而闻名,占乳腺癌病例的近四分之一。我们使用 HILIC-MS/MS 对三种细胞系及其培养基(包括 TNBC、非 TNBC 和正常乳腺上皮细胞)进行了 40 种氨基酸和衍生物的细胞内和细胞外分析。与非 TNBC 细胞相比,在 TNBC 细胞中观察到氨基酸和衍生物的特征性代谢改变,尤其是在相关的细胞内和细胞外代谢途径中。在细胞内,定量的谷氨酸、β-丙氨酸、天冬氨酸、谷胱甘肽、N-乙酰-丝氨酸和N-乙酰-甲硫氨酸增加最显着(>2 倍,p< 0.01 和 VIP > 1) 在 TNBC 细胞中。在细胞外,TNBC 细胞从细胞培养物中观察到谷氨酰胺、丝氨酸、β-丙氨酸和赖氨酸的摄取显着增加,谷氨酸和L-半胱氨酸-谷胱甘肽的排泄增加(p < 0.01 和 VIP > 1)媒体。这项研究描绘了 TNBC 和非 TNBC 细胞之间代谢失调的新动态描述,与细胞内和细胞外氨基酸谱相关。TNBC 细胞的这些独特代谢物的定量可能为 TNBC 提供先进的理解和新的治疗目标。