Establishment and molecular characterization of cell lines from Japanese patients with malignant pleural mesothelioma

Suzawa,Ken; Yamamoto,Hiromasa; Murakami,Tomoyuki; Katayama,Hideki; Furukawa,Masashi; Shien,Kazuhiko; Hashida,Shinsuke; Okabe,Kazunori; Aoe,Keisuke; Soh,Junichi; Asano,Hiroaki; Tsukuda,Kazunori; Mimura,Yusuke; Toyooka,Shinichi; Miyoshi,Shinichiro

doi:10.3892/ol.2015.3955

Establishment and molecular characterization of cell lines from Japanese patients with malignant pleural mesothelioma

Authors:
- Ken Suzawa
- Hiromasa Yamamoto
- Tomoyuki Murakami
- Hideki Katayama
- Masashi Furukawa
- Kazuhiko Shien
- Shinsuke Hashida
- Kazunori Okabe
- Keisuke Aoe
- Junichi Soh
- Hiroaki Asano
- Kazunori Tsukuda
- Yusuke Mimura
- Shinichi Toyooka
- Shinichiro Miyoshi
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Affiliations: Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700‑8558, Japan, Department of Clinical Research, National Hospital Organization Yamaguchi‑Ube Medical Center, Ube, Yamaguchi 755‑0241, Japan, Department of Thoracic Surgery, National Hospital Organization Yamaguchi‑Ube Medical Center, Ube, Yamaguchi 755‑0241, Japan
Published online on: November 23, 2015 https://doi.org/10.3892/ol.2015.3955
Pages: 705-712

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Abstract

Malignant pleural mesothelioma (MPM) is an aggressive disease that is resistant to conventional therapies. Cell lines are useful models for studying the biological characteristics of tumors; therefore, the establishment of MPM cell lines is valuable for exploring novel therapeutic strategies for MPM. In the present study, 4 MPM cell lines (YUMC8, YUMC44, YUMC63, and YUMC64) were established, which consisted of 2 epithelioid and 2 sarcomatoid mesothelioma histological subtypes, from Japanese patients with MPM. The DNA methylation status, mutations, copy number gains, protein expression of representative genes, and the sensitivity to several drugs were examined in these 4 cell lines. Methylation of P16 was demonstrated in 3/4 cell lines, in which the protein expression of p16 was lost. Methylation of RASSF1A was observed in 3/4 cell lines. Copy number gains of EGFR, HER2 or MET were not detected in the 4 cell lines. Mutations in various genes, including EGFR, KRAS, HER2, BRAF, and PIK3CA, which are frequently detected in non‑small cell lung cancer, were not detected in the 4 cell lines. microRNA‑34b/c is a direct transcriptional target of p53 and is often silenced in MPM by promoter methylation. In the present study, miR‑34b/c was heavily methylated in 2/4 established MPM cell lines. For cell adhesion molecules, E‑cadherin expression was detected in the 2 epithelioid MPM cell lines, whereas N‑cadherin expression was detected in all 4 established cell lines by western blotting. Vimentin was strongly expressed in the 2 sarcomatoid MPM cell lines. None of the established MPM cell lines demonstrated significant responses to the drugs tested, including NVP‑AUY922, 17‑DMAG, Trichostatin A, and Vorinostat. Although novel molecular findings were not observed in the current characterization of these MPM cell lines, these lines will be useful for future extensive analyses of the biological behavior of MPM and the development of novel therapeutic strategies.

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