Pani Giovambattista, Giannoni Elisa, Galeotti Tommaso, Chiarugi Paola
Institute of General Pathology, Catholic University Medical School , Rome, Italy.
Antioxid Redox Signal. 2009 Nov;11(11):2791-806. doi: 10.1089/ars.2009.2739.
We review here current evidence on the role of reactive oxygen species (ROS) and of the intracellular redox state in governing crucial steps of the metastatic process, from cell detachment from the primary tumor to final colonization of the distant site. In particular, we discuss the redox-dependent aspects of cell glycolytic metabolism (Warburg effect), of cell juggling between different motility styles (epithelial-to-mesenchymal and mesenchymal-to-amoeboid transition), of cell resistance to anoikis and of cell interaction with the stromal components of the metastatic niche. Central to this overview is the concept that metastasis can be viewed as an integrated "escape program" triggered by redox changes and instrumental at avoiding oxidative stress within the primary tumor. In this novel perspective, metabolic, motility, and prosurvival choices of the cell along the entire metastatic process can be interpreted as exploiting redox-signaling cascades to monitor oxidative/reductive environmental cues and escape oxidative damage. We also propose that this theoretic framework be applied to "normal" evasion/invasion programs such as in inflammation and development. Furthermore, we suggest that the intimate connection between metastasis, inflammation, and stem cells results, at least in part, by the sharing of a common redox-dependent strategy for infiltration, survival, dissemination, and patterning.
我们在此回顾有关活性氧（ROS）和细胞内氧化还原状态在调控转移过程关键步骤中作用的当前证据，这些步骤涵盖从细胞脱离原发肿瘤到最终在远处位点定植。特别地，我们讨论细胞糖酵解代谢（瓦伯格效应）、细胞在不同运动方式（上皮-间质转化和间质-阿米巴样转变）之间转换、细胞对失巢凋亡的抗性以及细胞与转移微环境基质成分相互作用等方面的氧化还原依赖性。本综述的核心观点是，转移可被视为由氧化还原变化触发的一种综合“逃逸程序”，有助于避免原发肿瘤内的氧化应激。从这个新视角来看，细胞在整个转移过程中的代谢、运动和存活选择可被解释为利用氧化还原信号级联来监测氧化/还原环境线索并逃避氧化损伤。我们还提出，这一理论框架应应用于诸如炎症和发育等“正常”的逃避/侵袭程序。此外，我们认为转移、炎症和干细胞之间的紧密联系至少部分是由于它们共享一种依赖氧化还原的共同策略，用于浸润、存活、播散和模式形成。
