Low Concentration Microenvironments Enhance the Migration of Neonatal Cells of Glial Lineage.
Low Concentration Microenvironments Enhance the Migration of Neonatal Cells of Glial Lineage.
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DOI：
10.1007/s12195-012-0226-y
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发表时间：
2012-06
影响因子：
2.8
通讯作者：
Vazquez, Maribel
中科院分区：
文献类型：
--
作者：
Able, Richard A., Jr.;Ngnabeuye, Celestin;Beck, Cade;Holland, Eric C.;Vazquez, Maribel
胶质瘤已经显示出通过招募神经胶质前体细胞(GPC)来维持生长的能力，这被认为是由趋化线索驱动的。先前的研究表明，不同遗传背景的小鼠GPC能够复制人类疾病中的扩散模式。具有肿瘤旁分泌信号转化的遗传背景的GPC如何通过迁移对细胞外信号做出反应在很大程度上尚未被探索，并且仍然是利用GPC作为治疗靶点的限制因素。在这项研究中，我们利用微流控装置检测了三个基因改变的小鼠GPC群体对肿瘤条件培养液的趋化作用，以及对三种已知启动胶质瘤细胞趋化作用的生长因子的趋化作用：肝细胞生长因子、血小板衍生生长因子-BB和转化生长因子-α(转化生长因子-α)。我们的结果表明，所研究的GPC类型对同一配体的不同浓度表现出化学吸引和化学排斥，以及在高浓度梯度环境中存在超低配体浓度时促进迁移。这些发现有助于我们理解GPC在肿瘤生长和复发中所起的致病和支持作用，并指出GPC是治疗胶质瘤的潜在靶点。
Glial tumors have demonstrated abilities to sustain growth via recruitment of glial progenitor cells (GPCs), which is believed to be driven by chemotactic cues. Previous studies have illustrated that mouse GPCs of different genetic backgrounds are able to replicate the dispersion pattern seen in the human disease. How GPCs with genetic backgrounds transformed by tumor paracrine signaling respond to extracellular cues via migration is largely unexplored, and remains a limiting factor in utilizing GPCs as therapeutic targets. In this study, we utilized a microfluidic device to examine the chemotaxis of three genetically-altered mouse GPC populations towards tumor conditioned media, as well as towards three growth factors known to initiate the chemotaxis of cells excised from glial tumors: Hepatocyte Growth Factor (HGF), Platelet-Derived Growth Factor-BB (PDGF-BB), and Transforming Growth Factor-α (TGF-α). Our results illustrate that GPC types studied exhibited chemoattraction and chemorepulsion by different concentrations of the same ligand, as well as enhanced migration in the presence of ultra-low ligand concentrations within environments of high concentration gradient. These findings contribute towards our understanding of the causative and supportive roles that GPCs play in tumor growth and reoccurrence, and also point to GPCs as potential therapeutic targets for glioma treatment.
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血小板衍生的生长因子BB介导人间充质干细胞的性质因子神经胶质瘤。
影响因子：
4.8
作者：
Hata N;Shinojima N;Gumin J;Yong R;Marini F;Andreeff M;Lang FF
通讯作者：
Lang FF
影响因子：
10.5
作者：
Dai, C;Celestino, JC;Holland, EC
通讯作者：
Holland, EC
影响因子：
3.7
作者：
Higginbotham, Holden;Yokota, Yukako;Anton, E. S.
通讯作者：
Anton, E. S.
影响因子：
6.4
作者：
ENGEBRAATEN, O;BJERKVIG, R;LAERUM, OD
通讯作者：
LAERUM, OD
影响因子：
3.7
作者：
Fomchenko EI;Dougherty JD;Helmy KY;Katz AM;Pietras A;Brennan C;Huse JT;Milosevic A;Holland EC
通讯作者：
Holland EC