Epithelial-Mesenchymal Plasticity in the D-Meso-Sonobe Mesothelioma Cell Line: A Putative Model of Epithelial-Mesenchymal Transition in Mesothelioma.

Epithelial-mesenchymal transition (EMT) plays a crucial role in carcinogenesis, including mesothelioma. D-Meso-Sonobe is a deciduoid-type mesothelioma cell line with morphological features similar to those of epithelioid cells. Here, we report that D-Meso-Sonobe cells exhibit spindle cell mesenchymal features under continuous confluent culture conditions. The spindle cell mesenchymal D-Meso-Sonobe expresses zinc finger E-box-binding homeobox 1 (Zeb1), which is a master regulator of EMT in the nucleus. Xenoplanted D-Meso-Sonobe cells expressed nuclear Zeb1 and yes-associated protein at the cancer invasion front and focally expressed integrin subunit alpha V and actin alpha 2, which are molecular phenotypes acquired by EMT in mesothelioma. Subsequent RNA sequencing revealed that lysyl oxidase like 1 (LOXL1) was more highly expressed in cultured spindle mesenchymal D-Meso-Sonobe cells than in epithelioid cells. LOXL1 immunoreactivity was observed at the invasive front of xenoplanted D-Meso-Sonobe cells. The epithelial-mesenchymal plasticity of D-Meso-Sonobe cells may be applicable for the development of candidate molecular agents targeting EMT in mesothelioma.