Abstract |
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.
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.
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.
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).
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.
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