Neurofibromin knockdown in glioma cell lines is associated with changes in cytokine and chemokine secretion in vitro.
Neurofibromin knockdown in glioma cell lines is associated with changes in cytokine and chemokine secretion in vitro.
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DOI：
10.1038/s41598-018-24046-2
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发表时间：
2018-04-11
影响因子：
4.6
通讯作者：
Pieper RO
中科院分区：
文献类型：
--
作者：
Wood MD;Mukherjee J;Pieper RO
神经纤维蛋白-1肿瘤抑制基因(NF1)在大约20%的散发性胶质母细胞瘤(GBM)病例中发生改变。NF1缺陷的GBM通常表现出间充质基因的表达特征，提示NF1状态与肿瘤微环境有关。为了确定在NF1缺陷的胶质瘤中分泌的细胞因子/趋化因子的变化，我们将细胞因子阵列应用于siRNA介导的NF1基因敲除后的三个GBM细胞系的条件培养液中。我们发现，在这些细胞系的不同亚群中，血小板衍生生长因子AA(PDGF-AA)、几丁质酶-3样蛋白1(CHI3L1)、白细胞介素8(IL-8)和内毒素(ENG)的分泌增加。分泌与诱导相应的信使RNA有关，这表明了一种涉及转录上调的机制。相比之下，在未转化的永生化正常人星形胶质细胞中，NF1基因敲除后，PDGF-AA的分泌增加，而CHI3L1、ENG和IL-8的分泌减少或不变。对癌症基因组图谱的分析证实了胶质瘤NF1状态与肿瘤样本中的ENG和CHI3L1的关系。总体而言，这项研究确定了NF1缺陷的胶质瘤细胞分泌蛋白的候选变化，这些变化可能影响肿瘤微环境，并表明NF1缺失与肿瘤细胞CHI3L1和endoglin的产生增加之间存在直接联系，这两个因素与胶质母细胞瘤的间充质特性有关。
The neurofibromin-1 tumor suppressor gene (NF1) is altered in approximately 20% of sporadic glioblastoma (GBM) cases. NF1 deficient GBM frequently shows a mesenchymal gene expression signature, suggesting a relationship between NF1 status and the tumor microenvironment. To identify changes in the production of secreted cytokines/chemokines in NF1 deficient glioma, we applied cytokine arrays to conditioned media from a panel of three GBM cell lines after siRNA-mediated NF1 knockdown. We identified increased secretion of platelet-derived growth factor AA (PDGF-AA), chitinase-3-like protein 1 (CHI3L1), interleukin-8 (IL-8), and endoglin (ENG) in different subsets of these cell lines. Secretion was associated with induction of the corresponding messenger RNA, suggesting a mechanism involving transcriptional upregulation. By contrast, in non-transformed immortalized normal human astrocytes, PDGF-AA secretion was increased upon NF1 knockdown, while secreted CHI3L1, ENG, and IL-8 were reduced or unchanged. Analysis of The Cancer Genome Atlas confirmed a relationship between glioma NF1 status and ENG and CHI3L1 in tumor samples. Overall, this study identifies candidate changes in secreted proteins from NF1 deficient glioma cells that could influence the tumor microenvironment, and suggests a direct link between NF1 loss and increased tumor cell production of CHI3L1 and endoglin, two factors implicated in mesenchymal identity in glioblastoma.
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影响因子：
50.3
作者：
McGillicuddy LT;Fromm JA;Hollstein PE;Kubek S;Beroukhim R;De Raedt T;Johnson BW;Williams SM;Nghiemphu P;Liau LM;Cloughesy TF;Mischel PS;Parret A;Seiler J;Moldenhauer G;Scheffzek K;Stemmer-Rachamimov AO;Sawyers CL;Brennan C;Messiaen L;Mellinghoff IK;Cichowski K
通讯作者：
Cichowski K
影响因子：
11.2
作者：
See, Wendy L.;Tan, I-Li;Pieper, Russell O.
通讯作者：
Pieper, Russell O.
影响因子：
50.3
作者：
Phillips, HS;Kharbanda, S;Aldape, K
通讯作者：
Aldape, K
DOI：
10.1073/pnas.1600914113
发表时间：
2016-10-25
影响因子：
11.1
作者：
Nadim, Wissem Deraredj;Chaumont-Dubel, Severine;Morisset-Lopez, Severine
通讯作者：
Morisset-Lopez, Severine
DOI：
10.1097/nen.0b013e318165eb75
发表时间：
2008-03-01
影响因子：
3.2
作者：
Rodriguez, Fausto J.;Perry, Arie;Giannini, Caterina
通讯作者：
Giannini, Caterina