Cytological and molecular analysis of malignant mesothelioma cells and identification of its cancer stem cells

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Malignant mesothelioma is an aggressive tumor of serosal surfaces which is refractory to current treatment options. We analyzed cytological and molecular characteristics of mesothelioma cells to identify the stem cells that initiate its tumorogenesis. We first analyzed the apoptosis of mesothelioma cells induced by arsenic trioxide (As_2O_3), which is used clinically to treat acute promyelocytic leukemia. We found that As_2O_3 inhibited cell viability of a mesothelioma cell line, NCI-H2052. As_2O_3 induced apoptosis of NCI-H2052 cells, which was accompanied by activation of JNK1/2, ERK1/2 and caspase-3. As_2O_3 induced apoptosis of NCI-H2052 cells mainly through JNK1/2 activation, and ERK1/2 was involved in As_2O_3-induced apoptosis when JNK1/2 was inactivated. On the other hands, we found that PP2, a selective SFK inhibitor, induced apoptosis through a caspase-8 pathway in NCI-H28 cells which are resistant to As_2O_3. Fyn-deficiency is prerequisite for caspase-8-dependent apoptosis induced by SFK inhibitors in mesothelioma cells. In our search for cancer stem cells, we found that mesothelioma cells expressed CD318, which play a role in mesotheiloma.