title: Antitumor compound testing in glioblastoma organotypic brain cultures.
abstract: Glioblastoma multiforme (GBM) is the most common and most aggressive type of primary brain tumor. Identification of new therapeutic regimens is urgently needed. A major challenge remains the development of a relevant in vitro model system with the necessary capacity and flexibility to profile compounds. The authors have developed and characterized a 3D culture system of brain cells (brain Hi-Spot) where GBM-derived cells can be incorporated (GBM/brain Hi-Spot). Immuno-fluorescence and electrophysiological recordings demonstrate that brain Hi-Spots recapitulate many features of brain tissue. Within this tissue, GBM-derived cell growth is monitored using a fluorescence assay. GBM-derived cells growing in Hi-Spots form tumor nodules that display properties of GBM such as 5-Ala positive staining, an acidic environment, and tumor-surrounding astrocyte activation. Temozolomide inhibits GBM growth in brain Hi-Spots, but it is not effective in 2D cultures. Other chemotherapeutics that have proven to be inefficient in GBM treatment display low activity against GBM-derived cells growing in brain Hi-Spots in comparison to their activity against GBM 2D cultures. These findings suggest that GBM/brain Hi-Spots represent a simple system to culture cells derived from brain tumors in an orthotopic environment in vitro and that the system is reliable to test GBM targeting compounds.
authors.affiliation: Capsant Neurotechnologies, London, UK.
authors.forename: Thelma
authors.initials: T
authors.lastname: Biggs
authors.forename: Janet
authors.initials: J
authors.lastname: Foreman
authors.forename: Lars
authors.initials: L
authors.lastname: Sundstrom
authors.forename: Urs
authors.initials: U
authors.lastname: Regenass
authors.forename: Francois
authors.initials: F
authors.lastname: Lehembre
mesh_terms: D000622:Aminolevulinic Acid / Q000032:analysis; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D015194:Diffusion Chambers, Culture; D004354:Drug Screening Assays, Antitumor; D004594:Electrophysiology; D005455:Fluorescent Antibody Technique; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006651:Histocytochemistry; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D000622:Aminolevulinic Acid