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细胞培养介质中的靶向代谢组学揭示乳腺癌细胞对支链氨基酸的摄取增加。

Targeted metabolomics in the cell culture media reveals increased uptake of branched amino acids by breast cancer cells.

机构信息

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

出版信息

Anal Biochem. 2021 Jul 1;624:114192. doi: 10.1016/j.ab.2021.114192. Epub 2021 Apr 2.

DOI:10.1016/j.ab.2021.114192
PMID:33812922
Abstract

In addition to the altered amino acids in many cancer cells for their uncontrolled growth, targeted metabolomics in cell culture media could display a dynamic interaction between cancer cells and their micro-environments. Methodology for cell culture medium samples is different from that of cell lysates on sampling points, calculation and statistical analysis. Targeted profiling method of 40 amino acid and derivatives was validated and performed on cell culture medium samples from cell lines of HCC 1806 (breast cancer cell) and MCF-10A (normal breast epithelial cell). Different from the common up-regulation of amino acids in cancer cell lysates, significantly increased uptake (>2.5-fold, VIP>1 and p < 0.001) of branched amino acids was observed in the cell culture media from the breast cancer cells while acetylmethionine, cysteine-glutathione, glutathione, cysteine and glutamic acid were excreted significantly more by the cancer cells to their media. The characteristic metabolic changes of amino acid and derivatives in the cell culture media provide a dynamic portrayal for the interaction of the breast cancer cells, normal breast cells with their micro-environments, which helps to understand the underlying proliferation mechanism of breast cancer cells.

摘要

除了许多癌细胞中氨基酸的改变促进了其失控生长外,细胞培养介质中的靶向代谢组学还可以显示癌细胞与其微环境之间的动态相互作用。细胞培养介质样本的方法与细胞裂解物在采样点、计算和统计分析上的方法不同。针对 HCC 1806(乳腺癌细胞)和 MCF-10A(正常乳腺上皮细胞)细胞系的细胞培养介质样本,验证并执行了 40 种氨基酸及其衍生物的靶向分析方法。与癌细胞裂解物中常见的氨基酸上调不同,在乳腺癌细胞的细胞培养介质中观察到支链氨基酸的摄取显著增加(>2.5 倍,VIP>1 和 p<0.001),而乙酰蛋氨酸、半胱氨酸-谷胱甘肽、谷胱甘肽、半胱氨酸和谷氨酸则由癌细胞显著更多地排泄到其介质中。细胞培养介质中氨基酸及其衍生物的特征代谢变化为乳腺癌细胞、正常乳腺细胞与其微环境的相互作用提供了一个动态描述,有助于理解乳腺癌细胞增殖的潜在机制。

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