title: Glioblastoma cells release factors that disrupt blood-brain barrier features.
abstract: The blood-brain barrier (BBB), mediated by endothelial tight junctions, is defective in malignant gliomas such as glioblastoma, resulting in cerebral edema and contrast enhancement upon neuroradiological examination. The mechanisms underlying BBB breakdown are essentially unknown. Since non-neoplastic astrocytes are required to induce BBB features of cerebral endothelial cells, it is conceivable that malignant astrocytes have lost this ability due to dedifferentiation. Alternatively, glioma cells might actively degrade previously intact BBB tight junctions. To examine the latter hypothesis, we have employed a transepithelial electrical resistance breakdown assay using monolayers of the C7 subclone of Madin-Darby canine kidney (MDCK-C7) cells forming tight junctions similar to those of BBB endothelial cells. We found that glioblastoma primary cells co-cultured with the MDCK-C7 monolayer (without direct contact of the two cell types) resulted in marked breakdown of electrical resistance, whereas primary cultures derived from low-grade gliomas (fibrillary astrocytoma, oligoastrocytoma) showed delayed or no effects. These results suggest that malignant gliomas have acquired the ability to actively degrade tight junctions by secreting soluble factors, eventually leading to BBB disruption within invaded brain tissue.
authors.affiliation: Institute of Physiology-Nanolab, University Hospital Münster, Muenster, Germany.
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Schneider
authors.forename: Thomas
authors.initials: T
authors.lastname: Ludwig
authors.forename: Lars
authors.initials: L
authors.lastname: Tatenhorst
authors.forename: Stephan
authors.initials: S
authors.lastname: Braune
authors.forename: Hans
authors.initials: H
authors.lastname: Oberleithner
authors.forename: Volker
authors.initials: V
authors.lastname: Senner
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001932:Brain Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D002478:Cells, Cultured; D015194:Diffusion Chambers, Culture / Q000295:instrumentation; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D005909:Glioblastoma / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D013997:Time Factors
chemical_list: D008070:Lipopolysaccharides