Background: Free radicals and antioxidant enzymes (AOEs) may play a critical role in cell proliferation and in the resistance of malignant cells against cytotoxic drugs and radiation. Malignant mesothelioma is a resistant tumor with high levels of manganese superoxide dismutase, a central superoxide scavenging AOE. In the current study, the authors assessed the expression and prognostic role of catalase, an important hydrogen peroxide scavenging AOE, in malignant pleural mesothelioma.
Methods: Catalase expression was investigated by immunohistochemistry in 5 cases of nonmalignant healthy pleura and in tumor tissue of 32 mesothelioma patients, and by Western blot in 7 continuous human mesothelioma cell lines. The distribution of catalase in mesothelioma cells was assessed by immunoelectron microscopy. Furthermore, to investigate the effect of catalase inhibition in the drug resistance of these cells in vitro, the authors exposed mesothelioma cells with the highest catalase level to epirubicin with and without aminotriazole pretreatment.
Results: Nonmalignant mesothelial cells showed no catalase immunoreactivity whereas most mesothelioma cases (24 of 32, 75%) were catalase positive, 17 cases (53%) showing moderate or high expression. Higher catalase expression in mesothelioma was associated with a better prognosis, mean survival rate from diagnosis being 6 and 24 months for negative/low expression and moderate/high expression, respectively. Furthermore, a coordinately high expression of both manganese-superoxide dismutase (Mn-SOD) and catalase predicted even more favorable outcome of the mesothelioma patients. Catalase also could be detected in all mesothelioma cell lines, the most resistant cell line showing the highest protein expression and compartmentalization of catalase mainly to peroxisomes. Aminotriazole inhibition of catalase had a marginal effect on the toxicity caused by epirubicin.
Conclusions: Catalase may have multifactorial effects in malignant cells; high catalase and/or coordinated high expression of Mn-SOD and catalase may decrease tumor progression by modulating the cellular redox state, but enhanced antioxidant capacity of mesothelioma cells also may protect tumor cells against exogenous oxidants, at least in vitro.
Copyright 2001 American Cancer Society.