Inhibition of CXCR7 extends survival following irradiation of brain tumours in mice and rats.
Inhibition of CXCR7 extends survival following irradiation of brain tumours in mice and rats.
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DOI：
10.1038/bjc.2013.830
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发表时间：
2014-03-04
影响因子：
8.8
通讯作者：
Brown JM
中科院分区：
文献类型：
--
作者：
Walters MJ;Ebsworth K;Berahovich RD;Penfold ME;Liu SC;Al Omran R;Kioi M;Chernikova SB;Tseng D;Mulkearns-Hubert EE;Sinyuk M;Ransohoff RM;Lathia JD;Karamchandani J;Kohrt HE;Zhang P;Powers JP;Jaen JC;Schall TJ;Merchant M;Recht L;Brown JM
在多形性胶质母细胞瘤（GBM）的实验模型中，辐射（IR）诱导趋化因子CXCL 12/SDF-1的局部表达，这促进了肿瘤复发。CXCR 7（CXCL 12的高亲和力受体）在肿瘤对IR的反应中的作用尚未得到解决。我们在三种啮齿动物GBM模型中测试了CXCR 7抑制剂对肿瘤生长和/或IR后动物存活的影响。我们使用免疫组织化学来确定CXCR 7蛋白在肿瘤和人类GBM样本中的表达。我们使用人GBM异种移植物的神经球形成测定来确定CXCR 7是否是体外癌症干细胞（CSC）活性所需的。在啮齿动物模型和人GBM中的肿瘤细胞和/或肿瘤相关脉管系统上检测到CXCR 7。在人GBM中，CXCR 7表达随着胶质瘤分级而增加，并且与CXCL 12和CXCL 11/I-TAC在空间上相关。在啮齿动物GBM模型中，IR后CXCR 7的药理学抑制引起肿瘤消退、阻断肿瘤复发和/或显著延长存活。人GBM异种移植细胞上的CXCR 7表达水平与神经球形成活性相关，并且CXCR 7抑制剂阻断了分选的CSC的球体形成。这些结果表明，CXCR 7抑制剂可能通过干扰CSC来阻断IR后GBM肿瘤复发。
In experimental models of glioblastoma multiforme (GBM), irradiation (IR) induces local expression of the chemokine CXCL12/SDF-1, which promotes tumour recurrence. The role of CXCR7, the high-affinity receptor for CXCL12, in the tumour's response to IR has not been addressed. We tested CXCR7 inhibitors for their effects on tumour growth and/or animal survival post IR in three rodent GBM models. We used immunohistochemistry to determine where CXCR7 protein is expressed in the tumours and in human GBM samples. We used neurosphere formation assays with human GBM xenografts to determine whether CXCR7 is required for cancer stem cell (CSC) activity in vitro. CXCR7 was detected on tumour cells and/or tumour-associated vasculature in the rodent models and in human GBM. In human GBM, CXCR7 expression increased with glioma grade and was spatially associated with CXCL12 and CXCL11/I-TAC. In the rodent GBM models, pharmacological inhibition of CXCR7 post IR caused tumour regression, blocked tumour recurrence, and/or substantially prolonged survival. CXCR7 expression levels on human GBM xenograft cells correlated with neurosphere-forming activity, and a CXCR7 inhibitor blocked sphere formation by sorted CSCs. These results indicate that CXCR7 inhibitors could block GBM tumour recurrence after IR, perhaps by interfering with CSCs.
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影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
胶质瘤干细胞增殖和肿瘤生长由一氧化氮合酶2促进。
影响因子：
64.5
作者：
Eyler CE;Wu Q;Yan K;MacSwords JM;Chandler-Militello D;Misuraca KL;Lathia JD;Forrester MT;Lee J;Stamler JS;Goldman SA;Bredel M;McLendon RE;Sloan AE;Hjelmeland AB;Rich JN
通讯作者：
Rich JN
DOI：
10.4161/cc.8.20.9701
发表时间：
2009-10-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Heddleston JM;Li Z;McLendon RE;Hjelmeland AB;Rich JN
通讯作者：
Rich JN
DOI：
10.1084/jem.20102010
发表时间：
2011-02-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cruz-Orengo L;Holman DW;Dorsey D;Zhou L;Zhang P;Wright M;McCandless EE;Patel JR;Luker GD;Littman DR;Russell JH;Klein RS
通讯作者：
Klein RS
影响因子：
50.3
作者：
Ahn, G-One;Brown, J. Martin
通讯作者：
Brown, J. Martin