title: Aligned chitosan-polycaprolactone polyblend nanofibers promote the migration of glioblastoma cells.
abstract: In vitro models that accurately mimic the microenvironment of invading glioblastoma multiform (GBM) cells will provide a high-throughput system for testing potential anti-invasion therapies. Here, the ability of chitosan-polycaprolactone polyblend nanofibers to promote a migratory phenotype in human GBM cells by altering the nanotopography of the nanofiber membranes is investigated. Fibers are prepared with diameters of 200 nm, 400 nm, and 1.1 μm, and are either randomly oriented or aligned to produce six distinct nanotopographies. Human U-87 MG GBM cells, a model cell line commonly used for invasion assays, are cultured on the various nanofibrous substrates. Cells show elongation and alignment along the orientation of aligned fibers as early as 24 h and up to 120 h of culture. After 24 h of culture, human GBM cells cultured on aligned 200 nm and 400 nm fibers show marked upregulation of invasion-related genes including β-catenin, Snail, STAT3, TGF-β, and Twist, suggesting a mesenchymal change in these migrating cells. Additionally, cells cultured on 400 nm aligned fibers show similar migration profiles as those reported in vivo, and thus these nanofibers should provide a unique high-throughput in vitro culture substrate for developing anti-migration therapies for the treatment of GBM.
authors.affiliation: Department of Materials Science and Engineering, University of Washington, Seattle, WA 98195, USA; Department of Neurological Surgery, University of Washington, Seattle, WA 98195, USA.
authors.forename: Forrest M
authors.initials: FM
authors.lastname: Kievit
authors.forename: Ashleigh
authors.initials: A
authors.lastname: Cooper
authors.forename: Soumen
authors.initials: S
authors.lastname: Jana
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Leung
authors.forename: Kui
authors.initials: K
authors.lastname: Wang
authors.forename: Dennis
authors.initials: D
authors.lastname: Edmondson
authors.forename: David
authors.initials: D
authors.lastname: Wood
authors.forename: Jerry S H
authors.initials: JS
authors.lastname: Lee
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ellenbogen
authors.forename: Miqin
authors.initials: M
authors.lastname: Zhang
mesh_terms: D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D057139:Nanofibers / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D011091:Polyesters; C016240:polycaprolactone; D048271:Chitosan
keywords: EMT; cancer; in vitro model; microenvironment; migration; nanofiber