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Oncol Lett. 2016 Jan;11(1):705-712. Epub 2015 Nov 23.

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

Author information

1
Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
2
Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; Department of Thoracic Surgery, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Yamaguchi 755-0241, Japan; Department of Clinical Research, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Yamaguchi 755-0241, Japan.
3
Department of Clinical Research, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Yamaguchi 755-0241, Japan.
4
Department of Clinical Research, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Yamaguchi 755-0241, Japan; Department of Medical Oncology, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Yamaguchi 755-0241, Japan.
5
Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; Department of Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
6
Department of Thoracic Surgery, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Yamaguchi 755-0241, Japan; Department of Clinical Research, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Yamaguchi 755-0241, Japan.

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.

KEYWORDS:

cell line; deletion; drug sensitivity; malignant pleural mesothelioma; methylation

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