Presence of human breast cancer xenograft changes the diurnal profile of amino acids in mice.
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Date
2022-01-19Author
Junior, RP
Sonehara, NM
Jardim-Perassi, BV
Pal, A
Asad, Y
Almeida Chuffa, LG
Chammas, R
Raynaud, FI
Zuccari, DAPC
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Cell Line
Cell Line, Tumor
Animals
Humans
Mice
Breast Neoplasms
Mammary Neoplasms, Experimental
Amino Acids
Pilot Projects
Neoplasm Transplantation
Circadian Rhythm
Female
Triple Negative Breast Neoplasms
Research team
Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
Language
eng
Date accepted
2022-01-04
License start date
2022-01-19
Citation
Scientific reports, 2022, 12 (1), pp. 1008 - ?
Publisher
NATURE PORTFOLIO