Graduate School of Comprehensive Human Sciences, Doctoral Program in Medical Sciences, University of Tsukuba, 1-1-1, Tennodai, Ibaraki, Tsukuba, 305-8575, Japan.
Department of Neurosurgery, Institute of Medicine, University of Tsukuba, 1-1-1, Tennodai, Ibaraki, Tsukuba, 305-8575, Japan.
Hum Cell. 2024 Nov 29;38(1):22. doi: 10.1007/s13577-024-01151-1.
Meningiomas are the most frequent brain tumors, typically benign and curable by surgery. However, some patients experience repeated recurrences from residual tumors. To address such cases, the development of novel therapeutic options is crucial. For this purpose, the availability of cell lines that possess the characteristics of benign meningiomas is essential. Here, we established a benign meningioma cell line under 3% O hypoxic conditions without the induction of immortalization genes. This cell line, named TKB-MEN2, has been stably grown for over two years with more than 20 passages. There were no hotspot telomerase reverse transcriptase (TERT) promoter mutations or cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) homozygous deletions, which are genetic features typical of malignant meningiomas. Cultured under hypoxic conditions, this cell line showed fewer characteristics of cellular senescence, such as morphological changes, IL-6 secretion, and lower senescence-associated b-galactosidase activity, compared to the same cell line cultured under 20% O conditions. This immortalized non-transgenic cell line appears to reflect the characteristics of a genuine benign meningioma, potentially allowing the identification of new therapeutic targets and the development of novel therapies for benign meningiomas.
脑膜瘤是最常见的脑肿瘤,通常为良性,可通过手术治愈。然而,一些患者的残余肿瘤会反复复发。为了解决这些情况,开发新的治疗方法至关重要。为此,需要有具有良性脑膜瘤特征的细胞系。在这里,我们在没有诱导永生化基因的情况下,在 3%O 低氧条件下建立了良性脑膜瘤细胞系。该细胞系命名为 TKB-MEN2,已经稳定生长超过两年,传代超过 20 代。该细胞系没有热点端粒酶逆转录酶(TERT)启动子突变或周期蛋白依赖性激酶抑制剂 2A/2B(CDKN2A/2B)纯合缺失,这些都是恶性脑膜瘤的遗传特征。在低氧条件下培养时,与在 20%O 条件下培养的相同细胞系相比,该细胞系表现出较少的细胞衰老特征,如形态变化、IL-6 分泌和较低的衰老相关 b-半乳糖苷酶活性。这种永生化非转基因细胞系似乎反映了真正良性脑膜瘤的特征,可能有助于确定新的治疗靶点,并开发针对良性脑膜瘤的新疗法。