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用于筛选人多形性胶质母细胞瘤抗迁移药物的渐缩微管阵列平台。

Tapered microtract array platform for antimigratory drug screening of human glioblastoma multiforme.

机构信息

Department of Bio and Brain Engineering, KAIST, Daejeon, 305-701, Korea.

出版信息

Adv Healthc Mater. 2015 Feb 18;4(3):405-11. doi: 10.1002/adhm.201400384. Epub 2014 Sep 17.

Abstract

Understanding the effects of topographic characteristics on tumor cell migration is important for the development of new anti-migratory therapies. However, simplified in vitro culture systems often lead to inaccurate results regarding the efficacy of drugs. Histopathologically, glioblastoma multiform (GBM) cells migrate along the orientation of thin, elongated anatomical structures, such as white-matter tracts. Here, a tapered microtract array platform which mimics the anatomical features of brain tissue is introduced. This platform enables optimization of design for platform fabrication depending on topographic effects. By monitoring the migration of GBM cells on a simple tapered microtract, a saltatory migration resembling the migratory phenotype of human GBM cells in vivo is observed. The platform effectively induces the native characteristics and behavior of cells by topographic cues, allowing to observe the critical point for crawling to saltatory transition. Furthermore, this platform can be applied to efficiently screen anti-cancer drug by inhibiting associated signaling pathways on GBM cells. In conclusion, the microtract array platform reported here may provide a better understanding of the effects of topographic characteristics on cell migration, and may also be useful to determine the efficacy of antimigratory drugs for glioblastoma cells with cellular and molecular research and high-throughput screening.

摘要

了解地形特征对肿瘤细胞迁移的影响对于开发新的抗迁移疗法很重要。然而,简化的体外培养系统常常导致药物疗效的结果不准确。组织病理学上,多形性胶质母细胞瘤(GBM)细胞沿着白质束等薄而细长的解剖结构的方向迁移。这里,引入了一种模仿脑组织解剖特征的锥形微管阵列平台。该平台能够根据地形效应优化平台制造的设计。通过监测 GBM 细胞在简单的锥形微管上的迁移,观察到类似于体内人类 GBM 细胞迁移表型的跳跃式迁移。该平台通过地形线索有效地诱导细胞的固有特征和行为,从而观察到爬行到跳跃式转变的临界点。此外,该平台可用于通过抑制 GBM 细胞相关信号通路来有效筛选抗癌药物。总之,这里报道的微管阵列平台可能有助于更好地了解地形特征对细胞迁移的影响,并且可能有助于通过细胞和分子研究以及高通量筛选来确定抗迁移药物对胶质母细胞瘤细胞的疗效。

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