The expression and possible role of manganese superoxide dismutase in malignant pleural mesothelioma

Abstract

<div lang="en" class="abs"><p class="abs_header">Abstract</p><p>Manganese superoxide dismutase (MnSOD) is an important intracellular antioxidant enzyme, which has been suggested to play a role in tumour biology. In the present study, the expression and possible role of MnSOD in malignant pleural mesothelioma was investigated.</p><p>Mesothelial cells in healthy visceral pleural tissue showed no MnSOD immunoreactivity in five out of six cases, whereas moderate or high immunoreactivity for MnSOD was detected in 30 out of 42 (71%) cases of mesothelioma. Only two of the 21 cases with metastatic adenocarcinoma of the pleura showed moderate MnSOD immunoreactivity, the remaining 19 (90.5%) showing negative or weak reactivity (p < 0.001, by Fisher’s exact test compared to mesothelioma). The immunostaining of catalase, a hydrogen peroxide scavenging antioxidant enzyme, was detectable in 27 of the 35 (77%) mesothelioma cases studied, whereas all the five samples of healthy pleural mesothelium were negative. Reactive mesothelium showed positive immunoreactivity for MnSOD and catalase, suggesting that induction of these enzymes is not specific for mesothelioma.</p><p>Two continuous human mesothelioma cell lines showed higher MnSOD activity, immunoreactive protein and mRNA levels than non-malignant mesothelial cells. In addition, mesothelioma cells expressing the highest MnSOD levels had the highest levels of catalase and copper-zinc superoxide dismutase. The mitochondria of these cells expressed higher MnSOD and lower superoxide levels than non-malignant mesothelial cells. The mesothelioma cells with the highest antioxidant enzyme levels were most resistant to oxidant- and drug-induced injury and to drug-induced apoptosis compared to non-malignant mesothelial cells and mesothelioma cells with lower MnSOD and catalase levels.</p><p> The extent of cell proliferation and apoptosis of mesothelioma tissue were 14.1±13.2% and 1.1±1.2%, respectively. MnSOD expression was inversely associated with cell proliferation (p = 0.02 by t-test), and a tendency for a better prognosis among patients with moderate or strong MnSOD expression was demonstrated. Patients displaying a tumour with enhanced proliferation or apoptosis had a poorer prognosis (p < 0.001 by Log Rank test).</p><p>In conclusion, the MnSOD level is usually high in pleural mesothelioma, which may affect the proliferation and drug-resistance of mesothelioma cells. MnSOD immunostaining can thus possibly be used to distinguish mesothelioma from metastatic adenocarcinoma but not from reactive mesothelium.</p></div>