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NCC-DMM1-C1的建立与鉴定,一种新型的源自患者的促结缔组织增生性恶性胸膜间皮瘤细胞系。

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

作者信息

Noguchi Rei, Yoshimatsu Yuki, Ono Takuya, Sei Akane, Motoi Noriko, Yatabe Yasushi, Yoshida Yukihiro, Watanabe Shunichi, Kondo Tadashi

机构信息

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.

出版信息

Oncol Lett. 2022 Feb;23(2):64. doi: 10.3892/ol.2021.13182. Epub 2021 Dec 27.

DOI:10.3892/ol.2021.13182
PMID:35069873
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8756558/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7647/8756558/4d51e52e778a/ol-23-02-13182-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7647/8756558/8a0ecac41345/ol-23-02-13182-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7647/8756558/430e2ce8a04e/ol-23-02-13182-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7647/8756558/784c18279874/ol-23-02-13182-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7647/8756558/da740c68545b/ol-23-02-13182-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7647/8756558/e4c4013fefa0/ol-23-02-13182-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7647/8756558/4d51e52e778a/ol-23-02-13182-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7647/8756558/8a0ecac41345/ol-23-02-13182-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7647/8756558/430e2ce8a04e/ol-23-02-13182-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7647/8756558/784c18279874/ol-23-02-13182-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7647/8756558/da740c68545b/ol-23-02-13182-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7647/8756558/e4c4013fefa0/ol-23-02-13182-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7647/8756558/4d51e52e778a/ol-23-02-13182-g05.jpg

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