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

Our plain-English summary of Epithelial-Mesenchymal Plasticity in the D-Meso-Sonobe Mesothelioma Cell Line: A Putative Model of Epithelial-Mesenchymal Transition in Mesothelioma, by H. Okubo, Y. Hanamatsu, C. Saigo, et al (Thoracic Cancer, 2025).

The study

• Authors: H. Okubo, Y. Hanamatsu, C. Saigo, S. Hiroshi, T. Takeuchi
• Journal: Thoracic Cancer
• Published: 2025;16(10):e70091
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© 2025 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.

In plain English

This brief report described laboratory experiments on D-Meso-Sonobe, a cell line from a deciduoid-type mesothelioma. The authors wanted to see whether it could model epithelial-mesenchymal transition (EMT), a process in which cancer cells lose epithelial features and take on a mesenchymal, spindle-shaped form. The study did not examine asbestos or any other exposure. Cells grown to about 60% confluence looked epithelioid. After 36 hours of continuous full-confluent culture they became spindle-shaped, and they returned to the epithelioid form after passage. Spindle-shaped cells showed strong Zeb1, a regulator of EMT, in the nucleus. Epithelioid cells showed only weak Zeb1 in the cytoplasm. The cells were also injected under the skin of immunodeficient mice. In the resulting tumors, Zeb1 and YAP appeared mostly in the cytoplasm at the tumor center but in cell nuclei at the invasion front, where LOXL1 staining was also seen. RNA sequencing compared two epithelioid and two spindle-cell samples. The LOXL1 transcript was about 5.27-fold higher in the spindle cells. The authors concluded that D-Meso-Sonobe cells may be useful for screening candidate agents against cancerous EMT.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study (brief report) of a human mesothelioma cell line, grown in culture and as tumors implanted in mice, using staining, immunoblotting and RNA sequencing
• Who was studied: The deciduoid-type mesothelioma cell line D-Meso-Sonobe. The cells (5 × 10^6) were injected into the thigh soft tissue of 10-week-old male SCID-NOD mice; the number of mice is not stated. RNA sequencing was done on two epithelioid and two spindle-cell culture samples. The animal work was done at Gifu University, Japan.
• Exposure: No asbestos or other fiber exposure was studied. The experimental condition was cell culture density: continuous full-confluent culture for 36 hours, compared with passage at about 60% confluence.
• Main results:
  • Cells passaged at about 60% confluence had epithelioid features. After 36 hours of continuous full-confluent culture they showed spindle-cell mesenchymal features. The spindle cells became epithelioid again after passage culture.
  • Epithelioid cells barely showed Zeb1 in the cytoplasm. Spindle-cell mesenchymal cells strongly showed Zeb1 in the nucleus.
  • In the mouse tumors, Zeb1 was weak and cytoplasmic at the tumor center. It was strong and nuclear at the invasion front.
  • In the mouse tumors, YAP was mainly cytoplasmic at the center and nuclear at the invasion front. ITGAV and ACTA2 staining was focal.
  • By RNA sequencing, transcripts of Zeb1, YAP, integrin subunit alpha V, actin alpha 2 and LOXL1 were about 1.23-, 1.05-, 1.46-, 3.03- and 5.27-fold higher in spindle-shaped cells than in epithelioid cells. Statistical significance for each gene is not reported in the text.
  • LOXL1 staining was seen at the invasion front of the mouse tumors, where nuclear Zeb1 also accumulated.
• The authors' conclusion: The authors concluded that D-Meso-Sonobe cells may be useful for screening candidate molecular agents against cancerous EMT. They also suggested that the cells' EMT plasticity is at least partially driven by transcriptional events.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Carcinogenesis, Epithelioid, Spindle Cell.

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