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

TL;DR

This study shows that D-Meso-Sonobe mesothelioma cells can switch between epithelial and mesenchymal states, offering a model for understanding EMT in mesothelioma.

Contribution

The study identifies D-Meso-Sonobe as a novel model for EMT in mesothelioma and highlights LOXL1 as a potential target.

Findings

D-Meso-Sonobe cells display epithelial-mesenchymal plasticity under different culture conditions.

LOXL1 is highly expressed in mesenchymal D-Meso-Sonobe cells and at the invasive front in xenografts.

Nuclear Zeb1 and other EMT markers are present in mesenchymal D-Meso-Sonobe cells.

Abstract

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.

EMT plasticity of D‐Meso‐Sonobe cells D‐Meso‐Sonobe cells exhibited epithelioid features in passage culture at approximately 60% confluence (upper left), but became spindle‐cell mesenchymal cells after continuous full confluent culturing (upper right). LOXL1 immunoreactivity was found at the invasion front near muscle cells, while minimum staining was observed in the non‐invasion front (lower).

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