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Acta Neuropathologica

, Volume 100, Issue 3, pp 323–331 | Cite as

Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme

  • S. Liebner
  • A. Fischmann
  • G. Rascher
  • F. Duffner
  • E.-H. Grote
  • H. Kalbacher
  • H. Wolburg
Regular Paper

Abstract

The aim of the study was to characterize the interendothelial junctions in tumor microvessels of five cases of human glioblastoma multiforme. In addition to morphological analysis, tumors were screened for the expression of junctional proteins, such as occludin, claudin-1, ZO-1 and catenins. The expression of the tight junction protein claudin-1 was lost in the majority of tumor microvessels, whereas claudin-5 and occludin were significantly down-regulated only in hyperplastic vessels. As shown by freeze-fracture analysis, under the conditions of tumor growth tight junction particles of endothelial cells were almost exclusively associated with the exocytoplasmic fracture face, providing evidence for a switch of the particles from the protoplasmic to the external leaflet of the endothelial membrane. These results suggest a relationship between claudin-1 suppression and the alteration of tight junction morphology, which is likely to correlate with the increase of endothelial permeability. Underlining the undifferentiated state of tumor microvessels, plakoglobin, a crucial protein for mature endothelial junctions, was not detectable in most microvessels, whereas β-catenin was abundantly labeled. In this context, it is of particular interest that the majority of microvascular pericytes were negative for alpha-smooth muscle actin, which is a marker of differentiated pericytes, although pericytes were frequently found in electron micrographs. In conclusion, the data suggest that the increase in microvascular permeability in human gliomas, contributing to the clinically severe symptoms of brain edema, is a result of a dysregulation of junctional proteins.

Key words Glioma Blood-brain barrier Tight junction Claudin Pericytes 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • S. Liebner
    • 1
  • A. Fischmann
    • 1
  • G. Rascher
    • 1
  • F. Duffner
    • 2
  • E.-H. Grote
    • 2
  • H. Kalbacher
    • 3
  • H. Wolburg
    • 1
  1. 1.Institute of Pathology, University of Tübingen, Liebermeister Strasse 8, 72076 Tübingen, GermanyDE
  2. 2.Department of Neurosurgery, University of Tübingen, Hoppe-Seyler Strasse 3, 72076 Tübingen, GermanyDE
  3. 3.Medical and Natural Sciences Research Center, Ob dem Himmelreich 7, 72074 Tübingen, GermanyDE

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