Temozolomide decreases invasion of glioma stem cells by down-regulating TGF-β2.
Temozolomide decreases invasion of glioma stem cells by down-regulating TGF-β2.
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DOI：
10.3892/or.2011.1362
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发表时间：
2011-10
期刊：
影响因子：
4.2
通讯作者：
Dongyong Zhang;Zhitao Jing;B. Qiu;A. Wu;Yun-jie Wang
中科院分区：
文献类型：
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作者：
Dongyong Zhang;Zhitao Jing;B. Qiu;A. Wu;Yun-jie Wang
胶质瘤的特征是过度增殖、弥漫性浸润和免疫抑制。最近的研究表明，胶质瘤干细胞（GSC）的限制性群体在胶质瘤的侵袭性生长和复发中起着关键作用。转化生长因子（Transforming growth factor，TGF）-β2是恶性胶质瘤相关的免疫抑制介质，也影响促侵袭功能。替莫唑胺（TMZ）是一种新型的烷化剂，对恶性胶质瘤具有良好的抗肿瘤作用，但其对胶质细胞侵袭的影响尚不清楚。为了解决这个问题，我们开发了针对来自原代培养的神经胶质瘤细胞的神经球的研究，由于神经球可以在GSC中富集，我们可以检查TMZ是否抑制GSC的侵袭。TMZ可抑制TGF-β2介导的侵袭，并在mRNA和蛋白水平下调TGF-β2的表达。因此，这些结果表明TMZ作为化疗药物可以减少GSC的侵袭及其免疫抑制活性。TMZ可作为免疫调节剂用于胶质瘤治疗。
Gliomas are characterized by excessive proliferation, diffuse infiltration and immunosuppression. Recent studies implicate a key role for a restricted population of glioma stem cells (GSCs) in glioma invasive growth and recurrence. Transforming growth factor (TGF)-β2 is a mediator of immunosuppression associated with malignant glioma and also influences pro-invasive functions. Temozolomide (TMZ), is a new alkylating agent with promising antitumour efficacy for malignant gliomas, and the effect of TMZ on GSCs invasion has not been known. To address this issue, we developed studies aimed at neurospheres from primary cultured glioma cells, due to the fact that since neurospheres can be enriched in GSCs, we could examine whether TMZ inhibits the invasion of GSCs. TMZ reduced the TGF-β2-mediated invasion, and down-regulated TGF-β2 expression at the mRNA and protein levels. Thus, these results indicate that TMZ, as a chemotherapeutic agent, can reduce the invasion of GSCs and their immunosuppressive activity. TMZ may be used as an immunomodulating agent for glioma therapy.