Radiation-induced PGE2 sustains human glioma cells growth and survival through EGF signaling.

Radiation-induced PGE2 sustains human glioma cells growth and survival through EGF signaling.
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DOI:
10.18632/oncotarget.3160
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发表时间:
2015-03-30
期刊:
影响因子:
--
通讯作者:
Oliver L
Oliver L
中科院分区:
其他
文献类型:
--
作者:
Brocard E;Oizel K;Lalier L;Pecqueur C;Paris F;Vallette FM;Oliver L

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多形性胶质母细胞瘤(GBM)是成人最常见的脑癌。尽管GBM是最具放射抗性的肿瘤之一,但放射治疗(RT)是最有效的术后治疗方法。人们认为,肿瘤内死亡或垂死的细胞会通过人们知之甚少的机制促进对治疗的抵抗。我们已经评估了前列腺素E2 (PGE2),一种多功能生物活性脂质,在GBM放射抗性中的作用。我们使用了一种体外方法,使用来自代表性GBM患者的3D原代培养物。我们表明,受辐照的胶质瘤细胞产生和释放PGE2的重要数量独立于诱导细胞死亡。我们证明PGE2的加入通过其反式激活上皮生长因子受体(EGFR)和激活β-连环蛋白的能力增强细胞存活和增殖。事实上,PGE2可以替代EGF促进原代培养物的体外存活和生长,其作用可能是通过前列腺素E2受体EP2实现的。
Glioblastoma Multiforme (GBM) is the most common brain cancer in adults. Radiotherapy (RT) is the most effective post-operative treatment for the patients even though GBM is one of the most radio-resistant tumors. Dead or dying cells within the tumor are thought to promote resistance to treatment through mechanisms that are very poorly understood. We have evaluated the role of Prostaglandin E2 (PGE2), a versatile bioactive lipid, in GBM radio-resistance. We used an in vitro approach using 3D primary cultures derived from representative GBM patients. We show that irradiated glioma cells produced and released PGE2 in important quantities independently of the induction of cell death. We demonstrate that the addition of PGE2 enhances cell survival and proliferation though its ability to trans-activate the Epithelial Growth Factor receptor (EGFR) and to activate β-catenin. Indeed, PGE2 can substitute for EGF to promote primary cultures survival and growth in vitro and the effect is likely to occur though the Prostaglandin E2 receptor EP2.
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