Techna Institute for the Advancement of Technology for Health, University Health Network, 100 College Street, Toronto, ON, M5G 1P5, Canada.
Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON, M5G 1L7, Canada.
Anal Bioanal Chem. 2021 Apr;413(10):2655-2664. doi: 10.1007/s00216-020-03054-0. Epub 2020 Nov 27.
This review provides a summary of known molecular alterations in commonly used cancer models and strives to stipulate how they may affect ambient mass spectrometry profiles. Immortalized cell lines are known to accumulate mutations, and xenografts derived from cell lines are known to contain tumour microenvironment elements from the host animal. While the use of human specimens for mass spectrometry profiling studies is highly encouraged, patient-derived xenografts with low passage numbers could provide an alternative means of amplifying material for ambient MS research when needed. Similarly, genetic preservation of patient tissue seen in some organoid models, further verified by qualitative proteomic and transcriptomic analyses, may argue in favor of organoid suitability for certain ambient profiling studies. However, to choose the appropriate model, pre-evaluation of the model's molecular characteristics in the context of the research question(s) being asked will likely provide the most appropriate strategy to move research forward. This can be achieved by performing comparative ambient MS analysis of the disease model of choice against a small amount of patient tissue to verify concordance. Disease models, however, will continue to be useful tools to orthogonally validate metabolic states of patient tissues through controlled genetic alterations that are not possible with patient specimens.
这篇综述总结了常用癌症模型中已知的分子改变，并努力阐明它们可能如何影响环境质谱分析谱。众所周知，永生化细胞系会积累突变，而源自细胞系的异种移植物则含有来自宿主动物的肿瘤微环境成分。虽然强烈鼓励使用人类标本进行质谱分析研究，但当需要时，具有低传代数的患者来源异种移植物可以提供一种替代方法来扩增用于环境 MS 研究的材料。同样，一些类器官模型中观察到的患者组织的遗传保存，进一步通过定性蛋白质组学和转录组学分析得到验证，可能支持类器官适合某些环境分析研究。然而，为了选择合适的模型，在提出的研究问题的背景下预先评估模型的分子特征，可能会提供最适合的策略来推进研究。这可以通过对所选疾病模型进行比较环境 MS 分析，与少量患者组织进行验证，以验证一致性。然而，疾病模型将继续是有用的工具，通过不可能用患者标本实现的受控遗传改变，对患者组织的代谢状态进行正交验证。
