Panoply™ Human MSLN Over-expressing Stable Cell Line

Lung cancer and pleural mesothelioma are two of the most lethal cancers. Limited treatment options and a poor understanding of disease mechanisms contribute to the extremely poor prognosis of lung cancer and mesothelioma. Mesothelin (MSLN) is a plasma membrane differentiation antigen expressed at high levels in many human solid tumors, including 70% of lung cancers and nearly all mesotheliomas. Here, researchers demonstrate that MSLN plays a critical role in controlling the epithelial-mesenchymal transition (EMT) and stemness properties of human lung cancer and mesothelioma cells, which dictate their tumorigenic and metastatic potential. First, they found that MSLN is highly upregulated in non-small cell lung cancer (NSCLC) patient tissues and in lung cancer and mesothelioma cell lines. Second, genetic knockdown of MSLN significantly reduced anchorage-independent cell growth, tumorsphere formation, cell adhesion, migration, and invasion in vitro, as well as tumor formation and metastasis in vivo. Third, ectopic overexpression of MSLN induced a malignant phenotype in non-cancerous cells, supporting its role as an oncogene. Finally, mechanistic studies revealed that knockdown of MSLN reversed EMT and attenuated stem cell properties, in addition to inhibiting tumor growth and metastasis. These results suggest that MSLN plays an important role in controlling EMT and stem cell properties in human lung cancer and mesothelioma cells.

Here, researchers performed gene overexpression experiments to compare the effects of MSLN overexpression on the anchorage-independent growth, migration, and invasion of noncancerous MeT5A mesothelial cells. The results showed that control MeT5A cells formed few or no small colonies in soft agar, whereas MSLN-overexpressing cells (MeT5A/MSLN) formed multiple large colonies (Figures 1a-c). Cell migration studies also demonstrated that MSLN-overexpressing cells were more migratory and invasive than control cells (Figures 1d-g). Together, these findings support a tumorigenic/metastatic role for MSLN in the tested cell systems.

Figure 1. Overexpression of MSLN promotes colony formation, cell migration, and invasion. (He X, et al., 2017)