Establishment and characterization of NCC-DMM1-C1, a novel patient-derived cell line of desmoplastic malignant pleural mesothelioma

摘要

Desmoplastic malignant pleural mesothelioma (DMM) is a rare histological variant of malignant pleural mesothelioma, which is a highly aggressive neoplasm of the mesothelium. DMM is associated with distant metastases and short survival. Effective treatments for DMM are not established and the development of histotype-tailored treatments is difficult due to the rarity of the disease. Although patient-derived cancer models are crucial tools for the development of novel therapeutics, they are difficult to obtain for DMM; no DMM cell lines or xenografts are available from public biobanks and only two cell lines have been reported. Thus, the present study aimed to establish a novel cell line of DMM as a resource for drug screening. A cell line of DMM was established, designated as NCC-DMM1-C1, using surgically resected tumor tissues from a 73-year-old male patient with DMM. Characteristics of NCC-DMM1-C1 cells were examined, such as growth, spheroid formation and invasion capability. Drug targets and anti-cancer drugs with anti-proliferative efficacy were examined using a comprehensive kinase activity assay and drug screening of 213 anti-cancer agents, respectively. NCC-DMM1-C1 exhibited fast growth, spheroid formation and invasion capability, suggesting that the NCC-DMM1-C1 cells retained the aggressive features of DMM. NCC-DMM1-C1 cells and the tumor tissue shared common activity profiles of kinases, which included FES, Wee1, platelet-derived growth factor receptor-β and Src. The drug screening revealed that bortezomib, fostamatinib, gemcitabine, homoharringtonine and vinorelbine had anti-proliferative effects, which have not been previously reported for DMM. It was concluded that NCC-DMM1-C1 cells may be a useful tool for the study of DMM.