Abstract 1684: Mesothelin regulates epithelial-to-mesenchymal transition and tumorigenicity of human lung cancer and mesothelioma cells

Lung cancer and malignant mesothelioma are two of the most deadly forms of cancers. The prognosis of lung cancer and mesothelioma is poor due to limited treatment modalities and lack of understanding of the underlying disease mechanisms. Mesothelin (MLSN), a plasma membrane differentiation antigen, is expressed at a high level in several human cancers, including 70% of lung cancer and nearly all mesotheliomas. Recent studies have shown that plasma and/or pleural effusion MSLN may be used as a biomarker for certain cancers and malignant pleural mesothelioma. However, the role of MLSN in lung cancer and mesothelioma is relatively unknown. In this study, we found that MLSN plays an important role in controlling epithelial-to-mesenchymal transition (EMT) and stem properties of human lung epithelial and mesothelial cells, which control their tumorigenicity. Firstly, MLSN was found to be highly upregulated in human non-small cell lung cancer tissues and in lung cancer and mesothelioma cells, as compared to normal tissues and non-tumorigenic lung epithelial and mesothelial cells. Secondly, knockdown of MLSN by RNA interference significantly reduced anchorage-independent cell growth, tumor sphere formation, and cell migration and invasion in vitro, as well as tumor formation in vivo. Thirdly, knockdown of MLSN attenuated cancer stem cell marker (ALDH) activity and several EMT markers in lung cancer and mesothelioma cell lines. These findings indicate the essential role of MLSN in EMT and malignant properties of human lung cancer and mesothelioma cells. Since EMT is an important process in tumor progression and metastasis, our finding on the role of MLSN may provide new insights into the disease mechanisms and treatment strategies for aggressive lung cancer and mesothelioma. Citation Format: Xiaoqing He, Liying Wang, Emily Despeaux, Yon Rojanasakul. Mesothelin regulates epithelial-to-mesenchymal transition and tumorigenicity of human lung cancer and mesothelioma cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1684.