title: Tapered microtract array platform for antimigratory drug screening of human glioblastoma multiforme.
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.
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, 305-701, Korea.
authors.forename: Junghwa
authors.initials: J
authors.lastname: Cha
authors.forename: Ilkyoo
authors.initials: I
authors.lastname: Koh
authors.forename: Yemuk
authors.initials: Y
authors.lastname: Choi
authors.forename: Jungwhoi
authors.initials: J
authors.lastname: Lee
authors.forename: Chulhee
authors.initials: C
authors.lastname: Choi
authors.forename: Pilnam
authors.initials: P
authors.lastname: Kim
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000814:Aniline Compounds / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D054443:Cell Migration Assays / Q000295:instrumentation / Q000379:methods*; D002465:Cell Movement; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation / Q000379:methods*; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D009570:Nitriles / Q000494:pharmacology; D000077191:Wortmannin
chemical_list: C539551:1,2,4,5-benzenetetraamine; D000730:Androstadienes; D000814:Aniline Compounds; D002070:Butadienes; D009570:Nitriles; C113580:U 0126; D000077191:Wortmannin
keywords: cancer drug screening; cell migration; glioblastoma multiforme (GBM); saltatory transition; tapered microtract array platform