Noguchi Rei, Yoshimatsu Yuki, Ono Takuya, Sei Akane, Motoi Noriko, Yatabe Yasushi, Yoshida Yukihiro, Watanabe Shunichi, Kondo Tadashi
Division of Rare Cancer Research, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan.
Oncol Lett. 2022 Feb;23(2):64. doi: 10.3892/ol.2021.13182. Epub 2021 Dec 27.
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.
促纤维增生性恶性胸膜间皮瘤(DMM)是恶性胸膜间皮瘤的一种罕见组织学变体,后者是一种具有高度侵袭性的间皮肿瘤。DMM与远处转移及生存期短相关。目前尚未确立针对DMM的有效治疗方法,且由于该疾病罕见,很难开发出针对特定组织学类型的治疗方法。尽管患者来源的癌症模型是开发新型疗法的关键工具,但对于DMM而言却很难获得;公共生物样本库中没有可用的DMM细胞系或异种移植模型,仅报道了两株细胞系。因此,本研究旨在建立一种新型DMM细胞系,作为药物筛选的资源。利用一名73岁患有DMM的男性患者手术切除的肿瘤组织,建立了一株DMM细胞系,命名为NCC-DMM1-C1。检测了NCC-DMM1-C1细胞的特性,如生长、球体形成和侵袭能力。分别使用全面激酶活性测定法和对213种抗癌药物的药物筛选,检测了药物靶点和具有抗增殖功效的抗癌药物。NCC-DMM1-C1表现出快速生长、球体形成和侵袭能力,表明NCC-DMM1-C1细胞保留了DMM的侵袭性特征。NCC-DMM1-C1细胞与肿瘤组织具有共同的激酶活性谱,其中包括FES、Wee1、血小板衍生生长因子受体-β和Src。药物筛选显示硼替佐米、福司他替尼、吉西他滨、高三尖杉酯碱和长春瑞滨具有抗增殖作用,这些作用此前尚未在DMM中报道过。得出的结论是,NCC-DMM1-C1细胞可能是研究DMM的有用工具。