Dudu Veronica, Able Richard A, Rotari Veronica, Kong Qingjun, Vazquez Maribel
Department of Biomedical Engineering, The City College of the City University of New York (CCNY), 160 Convent Ave., Steinman Hall Room 403D, New York, NY 10031, USA.
Cell Mol Bioeng. 2012 Dec;5(4):502-413. doi: 10.1007/s12195-012-0253-8.
Medulloblastoma (MB) is the most common brain cancer diagnosed among children. The cellular pathways that regulate MB invasion in response to environmental cues remain incompletely understood. Herein, we examine the migratory response of human MB-derived Daoy cells to different concentration profiles of Epidermal Growth Factor (EGF) using a microfluidic system. Our findings provide the first quantitative evidence that EGF concentration gradients modulate the chemotaxis of MB-derived cells in a dose-dependent manner the EGF receptor (EGF-R). Data illustrates that higher concentration gradients caused increased number of cells to migrate. In addition, our results show that EGF-induced receptor phosphorylation triggered the downstream activation of phosphoinositide-3 kinase (PI3K)/Akt pathway, while its downstream activation was inhibited by Tarceva (an EGF-R inhibitor), and Wortmannin (a PI3K inhibitor). The treatment with inhibitors also severely reduced the number of MB-derived cells that migrated towards increasing EGF concentration gradients. Our results provide evidence to bolster the development of anti-migratory therapies as viable strategies to impede EGF-stimulated MB dispersal.
髓母细胞瘤（MB）是儿童中最常见的被诊断出的脑癌。响应环境线索调节MB侵袭的细胞途径仍未完全了解。在此，我们使用微流控系统研究了源自人MB的Daoy细胞对不同浓度表皮生长因子（EGF）的迁移反应。我们的研究结果提供了首个定量证据，即EGF浓度梯度以剂量依赖方式调节源自MB的细胞的趋化性，通过表皮生长因子受体（EGF-R）。数据表明，更高的浓度梯度导致更多细胞迁移。此外，我们的结果表明，EGF诱导的受体磷酸化触发了磷酸肌醇-3激酶（PI3K）/Akt途径的下游激活，而其下游激活被特罗凯（一种EGF-R抑制剂）和渥曼青霉素（一种PI3K抑制剂）抑制。用抑制剂处理也严重减少了向增加的EGF浓度梯度迁移的源自MB的细胞数量。我们的结果为支持抗迁移疗法的发展提供了证据，作为阻碍EGF刺激的MB扩散的可行策略。
