Centre for Cancer Research, Monash Institute of Medical Research, Monash University, Victoria, Australia.
Antioxid Redox Signal. 2012 Jun 1;16(11):1229-47. doi: 10.1089/ars.2011.4489. Epub 2012 Mar 23.
Reactive oxygen species (ROS) such as superoxide, hydrogen peroxide, and peroxynitrite are generated ubiquitously by all mammalian cells and have been understood for many decades as inflicting cell damage and as causing cancer by oxidation and nitration of macromolecules, including DNA, RNA, proteins, and lipids.
A current concept suggests that ROS can also promote cell signaling pathways triggered by growth factors and transcription factors that ultimately regulate cell proliferation, differentiation, and apoptosis, all of which are important hallmarks of tumor cell proliferation and angiogenesis. Moreover, an emerging concept indicates that ROS regulate the functions of immune cells that infiltrate the tumor environment and stimulate angiogenesis, such as macrophages and specific regulatory T cells.
In this article, we highlight that the NADPH oxidase family of ROS-generating enzymes are the key sources of ROS and, thus, play an important role in redox signaling within tumor, endothelial, and immune cells thereby promoting tumor angiogenesis.
Knowledge of these intricate ROS signaling pathways and identification of the culprit NADPH oxidases is likely to reveal novel therapeutic opportunities to prevent angiogenesis that occurs during cancer and which is responsible for the revascularization after current antiangiogenic treatment.
活性氧（ROS）如超氧自由基、过氧化氢和过氧亚硝酸盐，普遍存在于所有哺乳动物细胞中，几十年来人们一直认为它们通过氧化和硝化大分子（包括 DNA、RNA、蛋白质和脂质）造成细胞损伤并导致癌症。
目前的一个概念表明，ROS 还可以促进生长因子和转录因子触发的细胞信号通路，这些通路最终调节细胞增殖、分化和凋亡，所有这些都是肿瘤细胞增殖和血管生成的重要标志。此外，一个新兴的概念表明，ROS 调节浸润肿瘤环境并刺激血管生成的免疫细胞的功能，如巨噬细胞和特定的调节性 T 细胞。
在本文中，我们强调 NADPH 氧化酶家族的 ROS 生成酶是 ROS 的主要来源，因此在肿瘤、内皮和免疫细胞中的氧化还原信号中发挥重要作用，从而促进肿瘤血管生成。
了解这些复杂的 ROS 信号通路，并确定罪魁祸首 NADPH 氧化酶，很可能揭示新的治疗机会，以阻止癌症发生时的血管生成，这是当前抗血管生成治疗后血管再形成的原因。
