High linear-energy-transfer radiation can overcome radioresistance of glioma stem-like cells to low linear-energy-transfer radiation.
High linear-energy-transfer radiation can overcome radioresistance of glioma stem-like cells to low linear-energy-transfer radiation.
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DOI：
10.1093/jrr/rrt095
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发表时间：
2014-01-01
影响因子：
2
通讯作者：
Miyatake S
中科院分区：
文献类型：
--
作者：
Hirota Y;Masunaga S;Kondo N;Kawabata S;Hirakawa H;Yajima H;Fujimori A;Ono K;Kuroiwa T;Miyatake S
电离辐射被用作多形性胶质母细胞瘤（GBM）的标准治疗。然而，放射治疗仍然仅仅是姑息性的，而不是治愈性的，因为胶质瘤干细胞（GSC）的存在，这被认为是高度放射抵抗低线性能量转移（LET）光子。在这里，我们分析了高LET颗粒是否可以克服GSC的辐射抗性。在干细胞培养基中从GBM细胞系A172诱导胶质瘤干细胞样细胞（GSLCs）。使用干细胞标记物确认GSLC和野生型细胞的表型。这些电池用60 Co γ射线或反应堆中子束辐照。在中子束辐照下，高LET质子粒子可以通过弹性散射或氮俘获反应产生。通过集落形成试验评估放射敏感性，并通过组蛋白γ-H2 AX焦点检测试验评估DNA双链断裂（DSB）。在干细胞培养液中，GSLCs可形成神经球样细胞，并表达丰富的神经干细胞标志物（Sox 2和Musashi）。GSLCs对伽马射线的抵抗力明显高于其亲本细胞，但中子束克服了这种抵抗力。有显着减少γ-H2 AX灶在A172 GSLCs与γ射线照射后24小时比在其亲本培养细胞，而中子束照射后没有明显的差异。高LET辐射可以通过产生不可修复的DNA双链断裂来克服GSLCs的辐射抗性。高LET放射治疗可能有潜力在临床环境中克服GBM对X射线的抵抗力。
Ionizing radiation is applied as the standard treatment for glioblastoma multiforme (GBM). However, radiotherapy remains merely palliative, not curative, because of the existence of glioma stem cells (GSCs), which are regarded as highly radioresistant to low linear-energy-transfer (LET) photons. Here we analyzed whether or not high-LET particles can overcome the radioresistance of GSCs. Glioma stem-like cells (GSLCs) were induced from the GBM cell line A172 in stem cell culture medium. The phenotypes of GSLCs and wild-type cells were confirmed using stem cell markers. These cells were irradiated with 60Co gamma rays or reactor neutron beams. Under neutron-beam irradiation, high-LET proton particles can be produced through elastic scattering or nitrogen capture reaction. Radiosensitivity was assessed by a colony-forming assay, and the DNA double-strand breaks (DSBs) were assessed by a histone gamma-H2AX focus detection assay. In stem cell culture medium, GSLCs could form neurosphere-like cells and express neural stem cell markers (Sox2 and Musashi) abundantly in comparison with their parental cells. GSLCs were significantly more radioresistant to gamma rays than their parental cells, but neutron beams overcame this resistance. There were significantly fewer gamma-H2AX foci in the A172 GSLCs 24 h after irradiation with gamma rays than in their parental cultured cells, while there was no apparent difference following neutron-beam irradiation. High-LET radiation can overcome the radioresistance of GSLCs by producing unrepairable DNA DSBs. High-LET radiation therapy might have the potential to overcome GBM's resistance to X-rays in a clinical setting.
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影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
放射抗性癌症干细胞中 AKT/cyclin D1/Cdk4 存活信号通路的激活。
影响因子：
6.2
作者：
Shimura, T.;Noma, N.;Oikawa, T.;Ochiai, Y.;Kakuda, S.;Kuwahara, Y.;Takai, Y.;Takahashi, A.;Fukumoto, M.
通讯作者：
Fukumoto, M.
影响因子：
3.8
作者：
Yamauchi, Motohiro;Oka, Yasuyoshi;Suzuki, Keiji
通讯作者：
Suzuki, Keiji
影响因子：
2.6
作者：
Leatherbarrow, EL;Harper, JV;O'Neill, P
通讯作者：
O'Neill, P
影响因子：
4.8
作者：
Ogden, Alfred T.;Waziri, Allen E.;Bruce, Jeffrey N.
通讯作者：
Bruce, Jeffrey N.