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Extracellular superoxide dismutase and its role in cancer.

ABSTRACT: Reactive oxygen species (ROS) are increasingly recognized as critical determinants of cellular signaling and a strict balance of ROS levels must be maintained to ensure proper cellular function and survival. Notably, ROS is increased in cancer cells. The superoxide dismutase family plays an essential physiological role in mitigating deleterious effects of ROS. Due to the compartmentalization of ROS signaling, EcSOD, the only superoxide dismutase in the extracellular space, has unique characteristics and functions in cellular signal transduction. In comparison to the other two intracellular SODs, EcSOD is a relatively new comer in terms of its tumor suppressive role in cancer and the mechanisms involved are less well understood. Nevertheless, the degree of differential expression of this extracellular antioxidant in cancer versus normal cells/tissues is more pronounced and prevalent than the other SODs. A significant association of low EcSOD expression with reduced cancer patient survival further suggests that loss of extracellular redox regulation promotes a conducive microenvironment that favors cancer progression. The vast array of mechanisms reported in mediating deregulation of EcSOD expression, function, and cellular distribution also supports that loss of this extracellular antioxidant provides a selective advantage to cancer cells. Moreover, overexpression of EcSOD inhibits tumor growth and metastasis, indicating a role as a tumor suppressor. This review focuses on the current understanding of the mechanisms of deregulation and tumor suppressive function of EcSOD in cancer.

SUBMITTER: Griess B

PROVIDER: S-EPMC5685559 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Extracellular superoxide dismutase and its role in cancer.

Griess Brandon B Tom Eric E Domann Frederick F Teoh-Fitzgerald Melissa M

Free radical biology & medicine 20170824

Reactive oxygen species (ROS) are increasingly recognized as critical determinants of cellular signaling and a strict balance of ROS levels must be maintained to ensure proper cellular function and survival. Notably, ROS is increased in cancer cells. The superoxide dismutase family plays an essential physiological role in mitigating deleterious effects of ROS. Due to the compartmentalization of ROS signaling, EcSOD, the only superoxide dismutase in the extracellular space, has unique characteris ...[more]

PMID: 28842347

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Project description:An important issue in critical care medicine is the identification of ways to protect the lungs from oxygen toxicity and reduce systemic oxidative stress in conditions requiring mechanical ventilation and high levels of oxygen. One way to prevent oxygen toxicity is to augment antioxidant enzyme activity in the respiratory system. The current study investigated the ability of aerosolized extracellular superoxide dismutase (EC-SOD) to protect the lungs from hyperoxic injury. Recombinant human EC-SOD (rhEC-SOD) was produced from a synthetic cassette constructed in the methylotrophic yeast Pichia pastoris. Female CD-1 mice were exposed in hyperoxia (FiO2>95%) to induce lung injury. The therapeutic effects of EC-SOD and copper-zinc SOD (CuZn-SOD) via an aerosol delivery system for lung injury and systemic oxidative stress at 24, 48, 72 and 96 h of hyperoxia were measured by bronchoalveolar lavage, wet/dry ratio, lung histology, and 8-oxo-2'-deoxyguanosine (8-oxo-dG) in lung and liver tissues. After exposure to hyperoxia, the wet/dry weight ratio remained stable before day 2 but increased significantly after day 3. The levels of oxidative biomarker 8-oxo-dG in the lung and liver were significantly decreased on day 2 (P<0.01) but the marker in the liver increased abruptly after day 3 of hyperoxia when the mortality increased. Treatment with aerosolized rhEC-SOD increased the survival rate at day 3 under hyperoxia to 95.8%, which was significantly higher than that of the control group (57.1%), albumin treated group (33.3%), and CuZn-SOD treated group (75%). The protective effects of EC-SOD against hyperoxia were further confirmed by reduced lung edema and systemic oxidative stress. Aerosolized EC-SOD protected mice against oxygen toxicity and reduced mortality in a hyperoxic model. The results encourage the use of an aerosol therapy with EC-SOD in intensive care units to reduce oxidative injury in patients with severe hypoxemic respiratory failure, including acute respiratory distress syndrome (ARDS).

Dataset Information

Extracellular superoxide dismutase and its role in cancer.

Publications

Extracellular superoxide dismutase and its role in cancer.

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