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

Abstract

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. IntroductionMalignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis, arising from mesothelial cells in the pleural cavity (1). Exposure to asbestos is closely associated with the development of MPM (2). MPM is historically a rare disease; however, the incidence of MPM is predicted to increase due to the use of asbestos worldwide and the long latency period for the development of MPM following exposure (3). Multimodality therapy that is centered on surgical resection is indicated for the treatment of MPM in the early stage (4). However, MPM is often diagnosed at an advanced stage, and it is known to be refractory to conventional therapies, such as surgery, chemotherapy, and radiotherapy (1). Therefore, novel strategies for the diagnosis and treatment of MPM are needed. However, much less information is available for MPM compared with other solid neoplasms. Thus, it is of great importance to investigate the biological behaviors of MPM.In the current study, 4 MPM cell lines were established from Japanese patients and the methylation statu...

Therapeutic potential of targeting S100A11 in malignant pleural mesothelioma

“…YUMC44 cell line was established by one of the authors (H.Y.) 30 . MSTO-211H, MeT-5A, N87 cell lines, seven lung cancer cell lines (HCC827, H1975, H1993, H1299, H460, H2170, and H157), three breast cancer cell lines (MCF-7, BT474, and SK-BR-3), and three colorectal cancer cell lines (Sw480, HT29, and DLD-1) were purchased from the American Type Culture Collection (Manassas, VA, USA).…”

Lentiviral vector-mediated transfection of human cancer cell lines with tumor suppressor genes inhibits proliferation in vitro

“…Abnormalities in the p16 gene have been observed in both NCI-H28 and NCI-H2052 cells [5,6], and Lenti-p16 had significant inhibitory effects on these cells ( Fig. 1A and 1B).…”