Glioma cells on the run - the migratory transcriptome of 10 human glioma cell lines.
Glioma cells on the run - the migratory transcriptome of 10 human glioma cell lines.
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DOI：
10.1186/1471-2164-9-54
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发表时间：
2008-01-29
期刊：
影响因子：
4.4
通讯作者：
Berens ME
中科院分区：
文献类型：
--
作者：
Demuth T;Rennert JL;Hoelzinger DB;Reavie LB;Nakada M;Beaudry C;Nakada S;Anderson EM;Henrichs AN;McDonough WS;Holz D;Joy A;Lin R;Pan KH;Lih CJ;Cohen SN;Berens ME
多形性胶质母细胞瘤（GBM）是最常见的原发性颅内肿瘤，尽管最近在治疗方案方面取得了进展，但受影响患者的预后仍然很差。GBM细胞的活跃细胞迁移和侵袭最终导致普遍存在的肿瘤复发和患者死亡。为了进一步了解神经胶质瘤细胞迁移能力的遗传机制，我们比较了人类神经胶质瘤细胞迁移和静止群体的匹配转录谱。使用单层径向迁移测定，从7个人长期胶质瘤细胞系和3个原代GBM培养物中分离运动和静止细胞群，并制备用于表达分析。使用将先验知识与表达数据相结合的模式识别方法来鉴定所有细胞系中的静止和迁移群体的基因表达特征。主成分分析（PCA）揭示了迁移和静止神经胶质瘤细胞之间的两种区分模式：i）全局下调和ii）全局上调谱，其用于GABRIEL中实施的基于先证者的规则函数中，以找到具有相似表达模式的基因子集。与正常脑相比，75%的人GBM活检标本中发现迁移性胶质瘤细胞中具有上调模式的基因过表达。开发了一种能够根据其迁移率对胶质瘤培养物进行分类的22个基因签名。通过验证入侵候选基因结缔组织生长因子（CTGF）来评估该发现算法的保真度。siRNA介导的敲低产生减少的体外迁移和离体侵袭;胶质瘤侵袭组织微阵列上的免疫组织化学证实了侵袭性胶质瘤细胞中CTGF的上调。诱导分散在体外的迁移性胶质瘤细胞的基因表达谱分析提供了基因组特征的发现;在转录和翻译水平以及通过功能测定对所选候选物进行了临床验证，从而强调了发现算法的保真度。
Glioblastoma multiforme (GBM) is the most common primary intracranial tumor and despite recent advances in treatment regimens, prognosis for affected patients remains poor. Active cell migration and invasion of GBM cells ultimately lead to ubiquitous tumor recurrence and patient death. To further understand the genetic mechanisms underlying the ability of glioma cells to migrate, we compared the matched transcriptional profiles of migratory and stationary populations of human glioma cells. Using a monolayer radial migration assay, motile and stationary cell populations from seven human long term glioma cell lines and three primary GBM cultures were isolated and prepared for expression analysis. Gene expression signatures of stationary and migratory populations across all cell lines were identified using a pattern recognition approach that integrates a priori knowledge with expression data. Principal component analysis (PCA) revealed two discriminating patterns between migrating and stationary glioma cells: i) global down-regulation and ii) global up-regulation profiles that were used in a proband-based rule function implemented in GABRIEL to find subsets of genes having similar expression patterns. Genes with up-regulation pattern in migrating glioma cells were found to be overexpressed in 75% of human GBM biopsy specimens compared to normal brain. A 22 gene signature capable of classifying glioma cultures based on their migration rate was developed. Fidelity of this discovery algorithm was assessed by validation of the invasion candidate gene, connective tissue growth factor (CTGF). siRNA mediated knockdown yielded reduced in vitro migration and ex vivo invasion; immunohistochemistry on glioma invasion tissue microarray confirmed up-regulation of CTGF in invasive glioma cells. Gene expression profiling of migratory glioma cells induced to disperse in vitro affords discovery of genomic signatures; selected candidates were validated clinically at the transcriptional and translational levels as well as through functional assays thereby underscoring the fidelity of the discovery algorithm.
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影响因子：
9.8
作者：
Johnston AL;Lun X;Rahn JJ;Liacini A;Wang L;Hamilton MG;Parney IF;Hempstead BL;Robbins SM;Forsyth PA;Senger DL
通讯作者：
Senger DL
影响因子：
56.9
作者：
Cukierman, E;Pankov, R;Yamada, KM
通讯作者：
Yamada, KM
影响因子：
5.7
作者：
Demuth, Tim;Reavie, Linsey B.;Berens, Michael E.
通讯作者：
Berens, Michael E.
DOI：
10.1152/ajpregu.00347.2002
发表时间：
2002-11-01
影响因子：
2.8
作者：
Ivanov, AI;Pero, RS;Romanovsky, AA
通讯作者：
Romanovsky, AA
影响因子：
11.2
作者：
Nakada, Mitsutoshi;Drake, Kelsey L.;Berens, Michael E.
通讯作者：
Berens, Michael E.