title: Proliferation and enrichment of CD133(+) glioblastoma cancer stem cells on 3D chitosan-alginate scaffolds.
abstract: Emerging evidence implicates cancer stem cells (CSCs) as primary determinants of the clinical behavior of human cancers, representing an ideal target for next-generation anti-cancer therapies. However CSCs are difficult to propagate in vitro, severely limiting the study of CSC biology and drug development. Here we report that growing cells from glioblastoma (GBM) cell lines on three dimensional (3D) porous chitosan-alginate (CA) scaffolds dramatically promotes the proliferation and enrichment of cells possessing the hallmarks of CSCs. CA scaffold-grown cells were found more tumorigenic in nude mouse xenografts than cells grown from monolayers. Growing in CA scaffolds rapidly promoted expression of genes involved in the epithelial-to-mesenchymal transition that has been implicated in the genesis of CSCs. Our results indicate that CA scaffolds have utility as a simple and inexpensive means to cultivate CSCs in vitro in support of studies to understand CSC biology and develop more effective anti-cancer therapies.
authors.affiliation: Department of Neurological Surgery, University of Washington, Seattle, WA 98195, USA.
authors.forename: Forrest M
authors.initials: FM
authors.lastname: Kievit
authors.affiliation: Department of Materials Science & Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Florczyk
authors.affiliation: Department of Materials Science & Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Leung
authors.affiliation: Department of Materials Science & Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Kui
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Wu
authors.affiliation: Department of Neurological Surgery, University of Washington, Seattle, WA 98195, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Silber
authors.affiliation: Department of Neurological Surgery, University of Washington, Seattle, WA 98195, USA; Department of Radiology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ellenbogen
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Center for Strategic Scientific Initiatives, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jerry S H
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Neurological Surgery, University of Washington, Seattle, WA 98195, USA; Department of Materials Science & Engineering, University of Washington, Seattle, WA 98195, USA. Electronic address: mzhang@u.washington.edu.
authors.forename: Miqin
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000464:Alginates / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005909:Glioblastoma; D020723:Glucuronic Acid / Q000737:chemistry / Q000494:pharmacology; D006603:Hexuronic Acids / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects*; D054457:Tissue Scaffolds / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000464:Alginates; D000970:Antineoplastic Agents; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D048271:Chitosan
keywords: Brain tumor initiating cells; Epithelial-to-mesenchymal transition; Hyaluronic acid; Microenvironment
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