Role of copper and SOD3-mediated extracellular redox regulation in tumor progression

Copper (Cu), an essential micronutrient, participates in several physiological processes, including cell proliferation and development. Notably, the disturbance of Cu homeostasis promotes tumor progression through the generation of oxidative stress. Chronic or excessive accumulation of reactive oxygen species (ROS) causes lipid peroxidation, protein denaturation, and enzyme inactivation, which leads to a breakdown of intracellular homeostasis and exacerbates tumor progression. The disruption of the ROS scavenging mechanism also reduces resistance to oxidative stress, leading to further deterioration in a disease state, and maintenance of redox homeostasis is thought to inhibit the onset and progression of various diseases. Superoxide dismutase 3 (SOD3), a Cu-containing secretory antioxidative enzyme, plays a key role in extracellular redox regulation, and the significant reduction in SOD3 facilitates tumor progression. Furthermore, the significant induction of SOD3 participates in tumor metastasis. This review focuses on the role of Cu homeostasis and antioxidative enzymes, including SOD3, in tumor progression, to help clarify the role of redox regulation.