High expression of estrogen receptor alpha and aromatase in glial tumor cells is associated with gender-independent survival benefits in glioblastoma patients
High expression of estrogen receptor alpha and aromatase in glial tumor cells is associated with gender-independent survival benefits in glioblastoma patients
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DOI：
10.1007/s11060-020-03467-y
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发表时间：
2020-04-02
影响因子：
3.9
通讯作者：
Delbridge, Claire
中科院分区：
文献类型：
--
作者：
Hoenikl, Lisa Stefanie;Laemmer, Friederike;Delbridge, Claire
多形性胶质母细胞瘤（GBM）是一种高度恶性的神经胶质肿瘤，男性比女性更常见。这种性别差异占主导地位的原因尚不清楚，这就提出了这些影响是否受激素控制的问题。本研究的目的是检查人GBM组织样本中雌激素受体α（ER α）和芳香化酶的表达与患者生存率的关系，并进一步研究标准化疗联合雌二醇治疗对体外胶质母细胞瘤肿瘤细胞系的影响。方法采用免疫组织化学方法检测60例GBM患者（男31例，女29例）组织中ER α和芳香化酶的表达，并进行生存分析。以不同剂量的17 β-雌二醇（E2）处理细胞株LN 18和LN 229，用MTT法测定细胞活力。在雌二醇预处理后，添加替莫唑胺并再次测试。结果ER α和芳香化酶在GBM组织样本中的高表达与GBM患者的生存时间显著延长相关，与性别和体重指数无关。与对照组相比，高浓度雌二醇治疗导致肿瘤细胞活力降低。雌二醇预处理后，细胞对替莫唑胺（TMZ）的敏感性显著增强。结论胶质瘤细胞的ER α表达似乎与芳香化酶的表达一样，作为GBM的生物标志物发挥重要的预后作用。标准化疗和雌二醇联合治疗GBM可能有利于患者的生存。
Introduction Glioblastoma multiforme (GBM) is a highly malignant glial tumor, affecting men more often than women. The reason for this gender-specific predominance remains unclear, raising the question whether these effects are subject to hormonal control. The purpose of this study was to examine the expression of estrogen receptor alpha (ER alpha) and aromatase in human GBM tissue samples in relation to patient survival and furthermore to investigate the effect of standard chemotherapy in combination with estradiol treatment on glioblastoma tumor cell lines in vitro. Methods 60 tissue samples (31 male, 29 female) of GBM patients were analysed with immunohistochemistry for ER alpha and aromatase for survival analyses. The cell lines LN18 and LN229 were treated with 17 beta-estradiol (E2) in different dosing regimens and the cell viability was measured with MTT assay. After estradiol pre-treatment Temozolomide was added and tested again. Results High expression of ER alpha and aromatase in the GBM tissue samples was associated with significantly longer survival times of GBM patients, regardless of gender and body-mass-index. The treatment with high concentrations of estradiol resulted in lower tumor cell viability, compared to control. The cells significantly showed a stronger sensitivity against Temozolomid (TMZ) after estradiol pre-treatment. Conclusion ER alpha-expression of glial tumour cells seems to play an important prognostic role as a biomarker in GBM, as well as the expression of the enzyme Aromatase. The combined treatment of GBM with standard chemotherapy and estradiol may be beneficial to patient's survival.