EGF as a New Therapeutic Target for Medulloblastoma Metastasis.
EGF as a New Therapeutic Target for Medulloblastoma Metastasis.
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EGF是髓母细胞瘤转移的新治疗靶标。
DOI：
10.1007/s12195-015-0395-6
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发表时间：
2015-12
影响因子：
2.8
通讯作者：
Vazquez M
中科院分区：
文献类型：
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作者：
Rico-Varela J;Singh T;McCutcheon S;Vazquez M
髓母细胞瘤（MB）是一种恶性小儿脑肿瘤，以其侵袭性转移潜力而闻名。尽管MB细胞迁移到大脑和脊柱的其他部分有充分的记录，MB趋化性知之甚少。在此，我们研究了MB衍生细胞对表皮生长因子（EGF）、肝细胞生长因子（HGF）、血小板衍生生长因子（PDGF-BB）和基质细胞衍生因子1-α（SDF-1）的外部信号传导的体外迁移和细胞反应。实验利用transwell分析和免疫细胞化学来识别MB迁移中的受体激活，并使用微流体平台来检查运动细胞的方向性、轨迹和梯度依赖性。数据表明，MB衍生的细胞强烈响应EGF的剂量和梯度依赖性的方式与增加的EGF-R激活，并显示，高EGF梯度场导致细胞迁移更长的定向距离的数量增加。我们的研究结果提供的证据表明，表皮生长因子及其受体发挥了重要的作用比以前记录的MB趋化迁移比以前记录的，并应考虑开发针对MB转移的迁移靶向治疗。
Medulloblastoma (MB) is a malignant pediatric brain tumor known for its aggressive metastatic potential. Despite the well-documented migration of MB cells to other parts of the brain and spinal column, MB chemotaxis is poorly understood. Herein, we examined the in vitro migratory and cellular responses of MB-derived cells to external signaling of Epidermal Growth Factor (EGF), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF-BB), and the stromal cell-derived factors 1-alpha (SDF-1). Experiments utilized transwell assays and immunocytochemistry to identify receptor activation in MB migration, and used a microfluidic platform to examine directionality, trajectory, and gradient-dependence of motile cells. Data illustrates that MB-derived cells respond strongly to EGF in a dosage and gradient-dependent manner with increased EGF-R activation, and show that high EGF gradient fields cause an increased number of cells to migrate longer directed distances. Our results provide evidence that EGF and its receptor play an important role than previously documented in MB chemotactic migration than previously documented and should be considered for developing migration-target therapies against MB metastasis.