Conventional Treatment of Glioblastoma Reveals Persistent CD44+Subpopulations
Conventional Treatment of Glioblastoma Reveals Persistent CD44+Subpopulations
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DOI：
10.1007/s12035-020-02004-2
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发表时间：
2020-07-06
影响因子：
5.1
通讯作者：
Andresen, Thomas Lars
中科院分区：
文献类型：
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作者：
Gudbergsson, Johann Mar;Christensen, Esben;Andresen, Thomas Lars
胶质母细胞瘤（GBM）是中枢神经系统最常见和最具破坏性的原发性肿瘤，诊断后的中位生存期为12至15个月。GBM由于其微妙的位置、肿瘤间和肿瘤内的异质性以及对治疗的高可塑性而非常难以治疗。在这项研究中，我们将原代GBM细胞颅内植入接受常规GBM治疗的小鼠中，包括辐射，替莫唑胺和组合。我们通过机械和酶促解离脑组织的组合获得单细胞悬液，并使用多色流式细胞术和聚类分析详细研究了GBM细胞响应体内常规治疗的变化。所有给药组中的CD44表达均升高，这通过随后的免疫组织化学证实。此外，高CD44表达与GBM和低级别胶质瘤（LGG）患者的不良预后相关。总之，这些结果表明CD44在胶质瘤发病机制中的关键作用。
Glioblastoma (GBM) is the most frequent and devastating primary tumor of the central nervous system with a median survival of 12 to 15 months after diagnosis. GBM is highly difficult to treat due to its delicate location, inter- and intra-tumoral heterogeneity, and high plasticity in response to treatment. In this study, we intracranially implanted primary GBM cells into mice which underwent conventional GBM treatments, including irradiation, temozolomide, and a combination. We obtained single cell suspensions through a combination of mechanical and enzymatic dissociation of brain tissue and investigated in detail the changes in GBM cells in response to conventional treatments in vivo using multi-color flow cytometry and cluster analysis. CD44 expression was elevated in all treatment groups, which was confirmed by subsequent immunohistochemistry. High CD44 expression was furthermore shown to correlate with poor prognosis of GBM and low-grade glioma (LGG) patients. Together, these results indicate a key role for CD44 in glioma pathogenesis.