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Acta Neuropathologica

, Volume 107, Issue 3, pp 272–276 | Cite as

Glioblastoma cells release factors that disrupt blood-brain barrier features

  • Stefan W. Schneider
  • Thomas Ludwig
  • Lars Tatenhorst
  • Stephan Braune
  • Hans Oberleithner
  • Volker Senner
  • Werner Paulus
Regular Paper

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.

keywords

Glioma Transepithelial electrical resistance Blood-brain barrier Permeability Cell culture model 

Notes

Acknowledgement

This study was supported by grant Pa 328/5 from Deutsche Forschungsgemeinschaft.

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Stefan W. Schneider
    • 1
    • 3
  • Thomas Ludwig
    • 1
  • Lars Tatenhorst
    • 2
  • Stephan Braune
    • 2
  • Hans Oberleithner
    • 1
  • Volker Senner
    • 2
  • Werner Paulus
    • 2
  1. 1.Institute of Physiology—NanolabUniversity Hospital MünsterMünsterGermany
  2. 2.Institute of NeuropathologyUniversity Hospital MünsterMünsterGermany
  3. 3.Department of DermatologyUniversity of MünsterMünsterGermany

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