Linking differential radiation responses to glioma heterogeneity.
Linking differential radiation responses to glioma heterogeneity.
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将差异辐射反应与神经胶质瘤异质性联系起来。
DOI：
10.18632/oncotarget.1823
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发表时间：
2014-03-30
期刊：
影响因子：
--
通讯作者：
Zhou YH
中科院分区：
文献类型：
--
作者：
Ke C;Tran K;Chen Y;Di Donato AT;Yu L;Hu Y;Linskey ME;Wang PH;Limoli CL;Zhou YH
定义高级别神经胶质瘤内肿瘤亚群的表型和遗传多样性可能导致治疗耐药和肿瘤复发。鉴于颅脑照射是恶性神经胶质瘤的一线治疗方法，了解照射如何选择性地影响这些异质癌症中的不同细胞亚群应有助于确定有针对性的干预措施，以更好地对抗这种致命疾病。为了分析不同神经胶质瘤亚群的放射反应，在促进粘附或非粘附球体的条件下培养 2 种神经胶质瘤细胞系（U251、A172）。过去的工作表明，来自特定培养条件的亚群在核型、增殖、基因表达和致瘤性方面表现出差异。发现来自每种神经胶质瘤细胞系的球状体培养物对放射更加敏感，这与照射后1周氧化应激水平较高以及氧化磷酸化和糖酵解代谢水平较低相一致。相比之下，抗辐射的非球状亲本培养物显示出响应辐射的糖酵解活性增加，而氧化磷酸化受到的影响较小。总体而言，这些数据表明，长时间的辐射诱导的氧化应激可能会损害某些神经胶质瘤亚群的代谢状态，从而改变它们对常规用于控制神经胶质瘤的重要治疗干预措施的敏感性。
The phenotypic and genetic diversity that define tumor subpopulations within high-grade glioma can lead to therapeutic resistance and tumor recurrence. Given that cranial irradiation is a frontline treatment for malignant glioma, understanding how irradiation selectively effects different cellular subpopulations within these heterogeneous cancers should help identify interventions targeted to better combat this deadly disease. To analyze the radiation response of distinct glioma subpopulations, 2 glioma cells lines (U251, A172) were cultured under conditions that promoted either adherence or non-adherent spheroids. Past work has demonstrated that subpopulations derived from defined culture conditions exhibit differences in karyotype, proliferation, gene expression and tumorigenicity. Spheroid cultures from each of the glioma cell lines were found to be more radiosensitive, which was consistent with higher levels of oxidative stress and lower levels of both oxidative phosphorylation and glycolytic metabolism 1 week following irradiation. In contrast, radioresistant non-spheroid parental cultures showed increased glycolytic activity in response to irradiation, while oxidative phosphorylation was affected to a lesser extent. Overall these data suggest that prolonged radiation-induced oxidative stress can compromise the metabolic state of certain glioma subpopulations thereby altering their sensitivity to an important therapeutic intervention used routinely for the control of glioma.
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影响因子：
3.7
作者：
Griguer CE;Oliva CR;Gobin E;Marcorelles P;Benos DJ;Lancaster JR Jr;Gillespie GY
通讯作者：
Gillespie GY
影响因子：
3.7
作者：
Sun Y;Kong W;Falk A;Hu J;Zhou L;Pollard S;Smith A
通讯作者：
Smith A
影响因子：
3.4
作者：
Limoli, CL;Giedzinski, E;Fike, JR
通讯作者：
Fike, JR
影响因子：
4.2
作者：
Nakano, Ichiro;Masterman-Smith, Michael;Kornblum, Harley I.
通讯作者：
Kornblum, Harley I.
影响因子：
2.6
作者：
Limoli, Charles L.;Giedzinski, Erich;Fike, John R.
通讯作者：
Fike, John R.