Kim Eunhye, Kim Mirae, So Kyungha, Park Young Seok, Woo Chang Gok, Hyun Sang-Hwan
Laboratory of Veterinary Embryology and Biotechnology (VETEMBIO), Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, 1 Chungdae-ro, Seowon-gu, Cheongju, 28644 Republic of Korea.
Institute for Stem Cell & Regenerative Medicine (ISCRM), Chungbuk National University, 1 Chungdae-ro, Seowon-gu, Cheongju, 28644 Republic of Korea.
Cancer Cell Int. 2020 Jul 28;20:345. doi: 10.1186/s12935-020-01438-x. eCollection 2020.
Meningiomas are the second most common primary tumors of the central nervous system. However, there is a paucity of data on meningioma biology due to the lack of suitable preclinical in vitro and in vivo models. In this study, we report the establishment and characterization of patient-derived, spontaneously immortalized cancer cell lines derived from World Health Organization (WHO) grade I and atypical WHO grade II meningiomas.
We evaluated high-resolution 3T MRI neuroimaging findings in meningioma patients which were followed by histological analysis. RT-qPCR and immunostaining analyses were performed to determine the expression levels of meningioma-related factors. Additionally, flow cytometry and sorting assays were conducted to investigate and isolate the CD133 and CD44 positive cells from primary atypical meningioma cells. Further, we compared the gene expression profiles of meningiomas and cell lines derived from them by performing whole-exome sequencing of the blood and tumor samples from the patients, and the primary cancer cell lines established from the meningioma tumor.
Our results were consistent with earlier studies that reported mutations in , , and genes in atypical meningiomas, and we also observed mutations in , a gene that was recently discovered. Significantly, the genomic signature was consistent between the atypical meningioma cancer cell lines and the tumor and blood samples from the patient.
Our results lead us to conclude that established meningioma cell lines with a genomic signature identical to tumors might be a valuable tool for understanding meningioma tumor biology, and for screening therapeutic agents to treat recurrent meningiomas.
脑膜瘤是中枢神经系统第二常见的原发性肿瘤。然而,由于缺乏合适的临床前体外和体内模型,关于脑膜瘤生物学的数据匮乏。在本研究中,我们报告了源自世界卫生组织(WHO)I级和非典型WHO II级脑膜瘤的患者来源的自发永生化癌细胞系的建立和特征。
我们评估了脑膜瘤患者的高分辨率3T MRI神经影像学结果,随后进行了组织学分析。进行了RT-qPCR和免疫染色分析以确定脑膜瘤相关因子的表达水平。此外,进行了流式细胞术和分选试验,以研究并从原发性非典型脑膜瘤细胞中分离出CD133和CD44阳性细胞。此外,我们通过对患者的血液和肿瘤样本以及从脑膜瘤肿瘤建立的原发性癌细胞系进行全外显子测序,比较了脑膜瘤及其衍生的细胞系的基因表达谱。
我们的结果与早期研究一致,早期研究报道了非典型脑膜瘤中 、 和 基因的突变,我们还观察到了最近发现的 基因的突变。重要的是,非典型脑膜瘤癌细胞系与患者的肿瘤和血液样本之间的基因组特征是一致的。
我们的结果使我们得出结论,具有与肿瘤相同基因组特征的已建立脑膜瘤细胞系可能是理解脑膜瘤肿瘤生物学以及筛选治疗复发性脑膜瘤的治疗药物的有价值工具。