Manganese Superoxide Dismutase (Sod2) and Redox-Control of Signaling Events That Drive Metastasis

Abstract

Manganese superoxide dismutase (Sod2) has emerged as a key enzyme with a dual role in tumorigenic progression. Early studies were primarily directed at defining the tumor suppressive function of Sod2 based on its low level expression in many tumor types. It is now commonly held that loss of Sod2 expression is likely an early event in tumor progression allowing for further propagation of the tumorigenic phenotype resulting from steady state increases in free radical production. Increases in free radical load have also been linked to defects in mitochondrial function and metastatic disease progression. It was initially believed that Sod2 loss may propagate metastatic disease progression, in reality both epidemiologic and experimental evidence indicate that Sod2 levels increase in many tumor types as they progress from early stage non-invasive disease to late stage metastatic disease. Sod2 overexpression in many instances enhances the metastatic phenotype that is reversed by efficient H2O2 scavenging. This review evaluates the many sequelae associated with increases in Sod2 that impinge on the metastatic phenotype. The ability to use Sod2 to modulate the cellular redox-environment has allowed for the identification of redox-responsive signaling events that drive malignancy, such as invasion, migration and prolonged tumor cell survival. Further studies of these redox-driven events will help in the development of targeted therapeutic strategies to efficiently restrict redox-signaling essential for malignant progression.

Relationships between chronic obstructive pulmonary disease and lung cancer: biological insights

“…Furthermore, in LC patients with COPD, the heaviest smokers were those showing the decrease in catalase levels in the tumor lesions compared to the nontumor lungs (26). These findings are consistent with other studies in which catalase deficiency was shown to contribute to mammary tumorigenesis in rodents (119) and cancer in patients (37). Collectively, it would be possible to conclude that catalase depletion seems to be involved in cancer development, especially in LC patients with underlying COPD, especially in those who were heavy smokers.…”

Redox Imbalance in Lung Cancer of Patients with Underlying Chronic Respiratory Conditions

“…In fact, a recent study (24) demonstrated that inhibition of SOD activity reduced tumor burden in mice and promoted cell death in several lines of NSCLC lines of cells. Furthermore, SOD2 was shown to favor cell migration and invasiveness of tumors in other investigations (43,44). More recently, mRNA and protein levels of SOD2 were also significantly increased in lung tumors and other cancer types in patients (25).…”

The Stance of Antioxidants in Brain Tumors

“…When tumor progresses more aggressive, MnSOD is upregulated. MnSOD level positively correlates with increased metastasis so MnSOD has an oncogene role (Hempel, et al, 2011;Dhar, et al, 2011). Increase in MnSOD level was seen during the progression of different types of tumors, including brain, to the metastatic stage.…”

“…The coexpression of catalase was shown to revert malignancy (Hempel, et al, 2011). The overexpression of catalase protected cancer cell from excessive peroxide production as a result of combined menadione/ascorbate anticancer treatment (Glorieux, et al, 2011).…”