Faculdade de Medicina de São José Do Rio Preto, São José do Rio Preto, Brazil.
The Institute of Cancer Research, London, UK.
Sci Rep. 2022 Jan 19;12(1):1008. doi: 10.1038/s41598-022-04994-6.
Human xenografts are extremely useful models to study the biology of human cancers and the effects of novel potential therapies. Deregulation of metabolism, including changes in amino acids (AAs), is a common characteristic of many human neoplasms. Plasma AAs undergo daily variations, driven by circadian endogenous and exogenous factors. We compared AAs concentration in triple negative breast cancer MDA-MB-231 cells and MCF10A non-tumorigenic immortalized breast epithelial cells. We also measured plasma AAs in mice bearing xenograft MDA-MB-231 and compared their levels with non-tumor-bearing control animals over 24 h. In vitro studies revealed that most of AAs were significantly different in MDA-MB-231 cells when compared with MCF10A. Plasma concentrations of 15 AAs were higher in cancer cells, two were lower and four were observed to shift across 24 h. In the in vivo setting, analysis showed that 12 out of 20 AAs varied significantly between tumor-bearing and non-tumor bearing mice. Noticeably, these metabolites peaked in the dark phase in non-tumor bearing mice, which corresponds to the active time of these animals. Conversely, in tumor-bearing mice, the peak time occurred during the light phase. In the early period of the light phase, these AAs were significantly higher in tumor-bearing animals, yet significantly lower in the middle of the light phase when compared with controls. This pilot study highlights the importance of well controlled experiments in studies involving plasma AAs in human breast cancer xenografts, in addition to emphasizing the need for more precise examination of exometabolomic changes using multiple time points.
人源异种移植瘤是研究人类癌症生物学和新型潜在治疗方法的非常有用的模型。代谢失调，包括氨基酸（AAs）的变化，是许多人类肿瘤的共同特征。受内源性和外源性昼夜节律因素的驱动，血浆 AAs 会发生日常变化。我们比较了三阴性乳腺癌 MDA-MB-231 细胞和 MCF10A 非致瘤性永生化乳腺上皮细胞中 AAs 的浓度。我们还测量了携带异种移植 MDA-MB-231 的小鼠的血浆 AAs，并在 24 小时内将其水平与非荷瘤对照动物进行了比较。体外研究表明，与 MCF10A 相比，MDA-MB-231 细胞中的大多数 AAs 差异显著。癌细胞中 15 种 AAs 的浓度较高，两种较低，四种在 24 小时内发生变化。在体内环境中，分析表明，在荷瘤和非荷瘤小鼠之间有 12 种 AAs 存在显著差异。值得注意的是，这些代谢物在非荷瘤小鼠的黑暗期达到峰值，这与这些动物的活跃时间相对应。相反，在荷瘤小鼠中，峰值时间出现在光照期。在光照早期，荷瘤动物的这些 AAs 明显升高，但在光照中期与对照组相比则明显降低。这项初步研究强调了在涉及人乳腺癌异种移植瘤血浆 AAs 的研究中进行严格控制实验的重要性，此外还强调了需要使用多个时间点更精确地检查外代谢组变化。
