Interleukin 32 Expression in Mesothelioma.

BACKGROUND

Interleukin 32 (IL32) has context-dependent roles in carcinogenesis across cancer types. In this study, we examined IL32 in mesotheliomas.

METHODS

IL32 protein expression was evaluated by immunohistochemistry in 56 mesothelioma tissue microarray specimens and by immunoblot analysis in cultured mesothelioma cell lines. The functional roles of IL32 were examined through ectopic expression of IL32β and IL32θ isoforms in D-Meso-Sonobe cells with epithelial-mesenchymal plasticity and through siRNA-mediated IL32 downregulation followed by cell-detachment-induced apoptosis assays in epithelioid mesothelioma cells.

RESULTS

IL32 immunoreactivity was detected in 20 of 56 mesothelioma tissue specimens, including cytoplasmic staining in 20 of 39 epithelioid cases, whereas little or no immunoreactivity was found in 17 sarcomatoid cases. In immunoblot analysis, an IL32 protein band was detected in two cultured epithelioid mesothelioma cell lines (MPM-2 and TCC-Meso-1), but not in sarcomatoid MPM-1 cells. Two IL32 isoforms, IL32β and IL32θ cDNAs, were isolated from MPM-2 cells. Ectopic expression of IL32θ, but not IL32β, inhibited the morphological transition from epithelioid to sarcomatoid features in D-Meso-Sonobe mesothelioma cells with mesothelial-mesenchymal transition plasticity. Conversely, siRNA-mediated downregulation of IL32 increased cell detachment-induced apoptosis in MPM-2 and TCC-Meso-1 epithelioid mesothelioma cells. Moreover, IL32 suppressed expression of secreted protein acidic and rich in cysteine, which is an epithelial-mesenchymal transition-related protein in mesothelioma cells.

CONCLUSIONS

These findings indicate that IL32 is expressed in epithelioid mesothelioma and may contribute to mesotheliomagenesis.