Arcucci Alessandro, Ruocco Maria Rosaria, Granato Giuseppina, Sacco Anna Maria, Montagnani Stefania
Department of Public Health, University of Naples Federico II, 80131 Naples, Italy.
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.
Biomed Res Int. 2016;2016:4502846. doi: 10.1155/2016/4502846. Epub 2016 Aug 9.
Redox balance is associated with the regulation of several cell signalling pathways and functions. In fact, under physiological conditions, cells maintain a balance between oxidant and antioxidant systems, and reactive oxygen species (ROS) can act as second messengers to regulate cell proliferation, cell death, and other physiological processes. Cancer tissues usually contain higher levels of ROS than normal tissues, and this ROS overproduction is associated with tumor development. Neoplastic tissues are very heterogeneous systems, composed of tumor cells and microenvironment that has a critical role in tumor progression. Cancer associated fibroblasts (CAFs) represent the main cell type of tumor microenvironment, and they contribute to tumor growth by undergoing an irreversible activation process. It is known that ROS can be transferred from cancer cells to fibroblasts. In particular, ROS affect the behaviour of CAFs by promoting the conversion of fibroblasts to myofibroblasts that support tumor progression and dissemination. Furthermore, the wrecking of redox homeostasis in cancer cells and tumor microenvironment induces a metabolic reprogramming in tumor cells and cancer associated fibroblasts, giving advantage to cancer growth. This review describes the role of ROS in tumor growth, by focusing on CAFs activation and metabolic interactions between cancer cells and stromal fibroblasts.
氧化还原平衡与多种细胞信号通路和功能的调节相关。事实上,在生理条件下,细胞维持着氧化剂和抗氧化剂系统之间的平衡,活性氧(ROS)可作为第二信使来调节细胞增殖、细胞死亡及其他生理过程。癌组织中的ROS水平通常高于正常组织,而这种ROS的过度产生与肿瘤发展相关。肿瘤组织是非常异质性的系统,由肿瘤细胞和在肿瘤进展中起关键作用的微环境组成。癌症相关成纤维细胞(CAF)是肿瘤微环境的主要细胞类型,它们通过经历不可逆的激活过程促进肿瘤生长。已知ROS可从癌细胞转移至成纤维细胞。特别是,ROS通过促进成纤维细胞向支持肿瘤进展和扩散的肌成纤维细胞转化来影响CAF的行为。此外,癌细胞和肿瘤微环境中氧化还原稳态的破坏会诱导肿瘤细胞和癌症相关成纤维细胞发生代谢重编程,从而有利于肿瘤生长。本综述通过聚焦CAF激活以及癌细胞与基质成纤维细胞之间的代谢相互作用,描述了ROS在肿瘤生长中的作用。