Establishment and biological characterization of cell line (FU-Meso-1) with malignant pleural mesothelioma

Abstract

Malignant mesotheliomas are rare malignant tumors, and cell lines from these rare tumors can be used as a substitute for fresh specimens for various tests, including cytogenetic and molecular biological studies. For the diagnosis of malignant pleural mesothelioma (MPM), the disappearance of BAP1 protein by immunohistochemical staining and homozygous deletion of CDKN2A by FISH help differentiate malignant mesothelial tumors from benign mesothelial proliferations. We established the cell line FU-Meso-1 from a thoracic tumor diagnosed histopathologically as biphasic MPM, and performed histopathological examinations, xenograft ability, and cytogenetic and molecular biological investigation of CDKN2A. Histological findings showed no epithelial-like components except in patient-derived tumor. Still, the patient-derived tumor, transplanted tumor, and FU-Meso-1 cell line all exhibited common immunohistological properties (carcinoma-positive markers negative, mesothelioma-positive markers positive), and the FU-Meso-1 cell line had xenograft ability. All materials showed CDKN2A heterozygous deletion by FISH, but RT-qPCR detected no CDKN2A expression. We subsequently detected methylation of the CDKN2A promoter region by methylation-specific PCR, resulting in FU-Meso-1 not expressing CDKN2A, and CDKN2A appeared to be a homozygous deleted.

As the FU-Meso-1 has characteristics similar to those of the patient-derived tumor, the FU-Meso-1 cell line will be useful for future extensive analyses of the biological behavior of MPM and the development of novel therapeutic strategies such as molecular targeted drugs and immunotherapy. A combination of FISH and RT-qPCR should be required to detect homozygous deletions of CDKN2A.