Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA; Michigan Institute for Computational Discovery and Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Pharmacol Ther. 2019 Dec;204:107398. doi: 10.1016/j.pharmthera.2019.107398. Epub 2019 Jul 31.
An estimated 70-90% of all cancers are linked to exposure to environmental risk factors. In parallel, the number of stem cells in a tissue has been shown to be a strong predictor of risk of developing cancer in that tissue. Tumors themselves are characterized by an acquisition of "stem cell" characteristics, and a growing body of evidence points to tumors themselves being sustained and propagated by a stem cell-like population. Here, we review our understanding of the interplay between environmental exposures, stem cell biology, and cancer. We provide an overview of the role of stem cells in development, tissue homeostasis, and wound repair. We discuss the pathways and mechanisms governing stem cell plasticity and regulation of the stem cell state, and describe experimental methods for assessment of stem cells. We then review the current understanding of how environmental exposures impact stem cell function relevant to carcinogenesis and cancer prevention, with a focus on environmental and occupational exposures to chemical, physical, and biological hazards. We also highlight key areas for future research in this area, including defining whether the biological basis for cancer disparities is related to effects of complex exposure mixtures on stem cell biology.
据估计，所有癌症中有 70%-90%与环境风险因素暴露有关。与此同时，组织中的干细胞数量已被证明是该组织发生癌症风险的强有力预测指标。肿瘤本身的特征是获得“干细胞”特征，越来越多的证据表明肿瘤本身是由类似于干细胞的群体维持和增殖的。在这里，我们回顾了我们对环境暴露、干细胞生物学和癌症之间相互作用的理解。我们概述了干细胞在发育、组织稳态和伤口修复中的作用。我们讨论了控制干细胞可塑性和干细胞状态调节的途径和机制，并描述了评估干细胞的实验方法。然后，我们回顾了目前对环境暴露如何影响与致癌和癌症预防相关的干细胞功能的理解，重点是化学、物理和生物危害的环境和职业暴露。我们还强调了该领域未来研究的重点领域，包括确定癌症差异的生物学基础是否与复杂暴露混合物对干细胞生物学的影响有关。
