The Pro-Metastatic Roles of ROS.

Metastasis is a complex, multistep process in which cancer spreads from its original tumor to other sites in the body. During metastasis, tumor cells move away from the primary tumor and intravasate into the lymphatics or circulation. Surviving tumor cells can then extravasate into and remain in distant tissues until they once again begin to proliferate, forming secondary tumors. An excess of reactive oxygen species (ROS) can promote metastasis, dependent on the ROS molecule, its level of excess, and the examined step within the metastatic cascade. Here, we highlight recent studies where ROS promote epithelial-to-mesenchymal transition, cell migration and invasion, circulating tumor cell survival and disseminated tumor cell dormancy. Additionally discussed are novel in vivo ROS detection methods, FDA-approved therapies and clinical trials that manipulate ROS to improve cancer patient survival. Since metastasis is the major cause of cancer-related death, a better understanding of this process and ROS as a contributing factor will help to identify novel targets for inhibition or prevention.