Jensen Lasse Dahl
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden; Department of Medical and Health Sciences, Linköpings University, 581 85 Linköping, Sweden.
Biochim Biophys Acta. 2015 Aug;1850(8):1633-41. doi: 10.1016/j.bbagen.2014.10.025. Epub 2014 Oct 25.
Cancer is considered to develop due to disruptions in the tissue microenvironment in addition to genetic disruptions in the tumor cells themselves. The two most important microenvironmental disruptions in cancer are arguably tissue hypoxia and disrupted circadian rhythmicity. Endothelial cells, which line the luminal side of all blood vessels transport oxygen or endocrine circadian regulators to the tissue and are therefore of key importance for circadian disruption and hypoxia in tumors.
Here I review recent findings on the role of circadian rhythms and hypoxia in cancer and metastasis, with particular emphasis on how these pathways link tumor metastasis to pathological functions of blood vessels. The involvement of disrupted cell metabolism and redox homeostasis in this context and the use of novel zebrafish models for such studies will be discussed.
Circadian rhythms and hypoxia are involved in tumor metastasis on all levels from pathological deregulation of the cell to the tissue and the whole organism. Pathological tumor blood vessels cause hypoxia and disruption in circadian rhythmicity which in turn drives tumor metastasis. Zebrafish models may be used to increase our understanding of the mechanisms behind hypoxia and circadian regulation of metastasis.
Disrupted blood flow in tumors is currently seen as a therapeutic goal in cancer treatment, but may drive invasion and metastasis via pathological hypoxia and circadian clock signaling. Understanding the molecular details behind such regulation is important to optimize treatment for patients with solid tumors in the future. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation.
癌症被认为是由于肿瘤细胞自身的基因破坏以及组织微环境的紊乱而发生发展的。癌症中两个最重要的微环境紊乱因素可以说是组织缺氧和昼夜节律紊乱。内皮细胞排列在所有血管的管腔侧，将氧气或内分泌昼夜调节因子输送到组织中，因此对于肿瘤中的昼夜节律紊乱和缺氧至关重要。
在此，我综述了昼夜节律和缺氧在癌症及转移中作用的最新研究发现，特别强调了这些途径如何将肿瘤转移与血管的病理功能联系起来。还将讨论在这种情况下细胞代谢紊乱和氧化还原稳态的参与以及新型斑马鱼模型在此类研究中的应用。
昼夜节律和缺氧在从细胞的病理失调到组织和整个生物体的各个层面都参与肿瘤转移。病理性肿瘤血管导致缺氧和昼夜节律紊乱，进而驱动肿瘤转移。斑马鱼模型可用于增进我们对缺氧和转移的昼夜调节背后机制的理解。
肿瘤中血流紊乱目前被视为癌症治疗的一个治疗目标，但可能通过病理性缺氧和昼夜节律信号传导驱动侵袭和转移。了解这种调节背后的分子细节对于未来优化实体瘤患者的治疗很重要。本文是名为“分化与去分化的氧化还原调节”的特刊的一部分。
