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用针对 IDH1R132H 的抗体证实的脑胶质瘤细胞的体外自发衰老。

Spontaneous in vitro senescence of glioma cells confirmed by an antibody against IDH1R132H.

机构信息

Department of Tumor Biology, Medical University of Lodz, Lodz, Poland

Clinical Department of Neurosurgery, The Voivodal Specialistic Hospital in Olsztyn, Olsztyn, Poland.

出版信息

Anticancer Res. 2014 Jun;34(6):2859-67.

PMID:24922649
Abstract

BACKGROUND

We have recently suggested that glioblastoma cells become spontaneously senescent in cell culture conditions. The antibody specific against IDH1(R132H) offers the perfect opportunity to verify this hypothesis.

MATERIALS AND METHODS

We analyzed the features of senescence in 8 glioma cell cultures showing the IDH1(R132H) mutation based on combination of immunocytochemistry, enzymo-cytochemistry, BrdU incorporation assay and real-time microscopic observation.

RESULTS

We report that glioma cells showing the IDH1(R132H) mutation become rapidly and spontaneously senescent in vitro. Senescence was observed in both classical and novel serum-free cell culture conditions. Importantly, the senescent IDH1(R132H)-positive cells showed the expression of stemness marker (SOX2).

CONCLUSION

In vitro senescence appeared to be the main reason of the difficulties in any kind culturing of glioma cells. 3D cell cultures prolonged the survival and in vitro proliferation of neoplastic IDH1(R132H)-positive cells, however, did not enhance the stabilization efficiency. Senescence of glioma cells is spontaneously triggered in vitro, which offers the opportunity of potential new therapeutic strategies based on this phenomenon.

摘要

背景

我们最近提出胶质母细胞瘤细胞在细胞培养条件下会自发衰老。针对 IDH1(R132H)的抗体为验证这一假说提供了绝佳机会。

材料与方法

我们分析了 8 种具有 IDH1(R132H)突变的神经胶质瘤细胞培养物的衰老特征,综合使用免疫细胞化学、酶细胞化学、BrdU 掺入检测和实时显微镜观察。

结果

我们报告称,具有 IDH1(R132H)突变的神经胶质瘤细胞在体外迅速自发衰老。在经典和新型无血清细胞培养条件下均观察到衰老。重要的是,衰老的 IDH1(R132H)阳性细胞表达了干性标志物(SOX2)。

结论

体外衰老似乎是培养神经胶质瘤细胞的主要困难原因。3D 细胞培养延长了肿瘤性 IDH1(R132H)阳性细胞的存活和体外增殖,但并未提高稳定性。神经胶质瘤细胞在体外自发衰老,为基于这一现象的潜在新治疗策略提供了机会。

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