Search

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.

Additional file 1: Supplemental information. C11orf95-RELA fusion drives aberrant gene expression through the unique epigenetic regulation for ependymoma formation. atsuya Ozawa, Syuzo Kaneko, Frank Szulzewsky, Zhiwei Qiao, Mutsumi Takadera, Yoshitaka Narita, Tadashi Kondo, Eric C. Holland, Ryuji Hamamoto, Koichi Ichimura. Table of Contents:Supplementary Figures S1-S6; Supplementary Figure legends; Supplementary Table legends. (DOCX 142 KB)

著者人数: 16名, Accepted: 2016-05-05, 資料番号: SA1160048000

The establishment of a model system of neoplastic transformation of normal human cells has been attempted with a chemical carcinogen, 4-nitroquinoline 1-oxide (4NQO). In the course of these experiments, it was noticed that immortalization of human cells is a multi-step process involving several mutational genetic events. Thus, chromosomal changes which occurred during the process of immortalization of human fibroblasts were examined. To accomplish immortalization, fibroblasts obtained from an embryo were repeatedly treated with 10-6M4NQO from primary culture to passage 51 (59 treatments in total). Before immortalization, some chromosomes (especially, chromosomes 2, 6, 8, 10, 11, 12, 15, 19, and 20), were lost at a relatively high frequency. After immortalization, the chromosomes distributed so broadly in the triploid to hypotetraploid region without a distinct modal number or without marker chromosomes that it was difficult to identify the specific chromosomes related to the immortalization of human cells. No specific structural chromosomal changes were detected. Although the significance of such chromosome changes in relation to immortalization is not clear, the loss of some specific chromosomes suggests that genes which are involved in cellular aging and which suppress immortalization may have been lost in the immortalization process.