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Dynamics of expression patterns of AQP4, dystroglycan, agrin and matrix metalloproteinases in human glioblastoma

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Abstract

In human glioblastoma, the blood–brain barrier (BBB) is disturbed. According to our concept, the glio-vascular relationships and thus the control of the BBB are essentially dependent on the polarity of astroglial cells. This polarity is characterized by the uneven distribution of the water channel protein aquaporin-4 (AQP4), dystroglycan and other molecules. Recently, we were able to show that the extracellular matrix component agrin is important for the construction and localization of the so-called orthogonal arrays of particles (OAPs), which consist in AQP4. Here, combining freeze-fracture electron microscopy, immunohistochemistry and Western blotting, we describe alterations of expression and distribution of AQP4, dystroglycan, agrin and the matrix metalloproteinases (MMP) 2, 3 and 9 in human primary glioblastomas (eight primary tumours, six recurrent tumours). Increase of MMP3- and MMP2/9 immunoreactivities went along with loss of agrin and dystroglycan respectively. On the protein level, AQP4 expression was increased in glioblastoma compared to control tissue. This was not accompanied by an increase of OAPs, suggesting that AQP4 can also occur without forming OAPs. The results underline our concept of the loss of glioma cell polarity as one of the factors responsible for the disturbance of the neurovascular unit and as an explanation for the formation of edemas in the glioblastoma.

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Acknowledgements

Yeliz Donat-Krasnici, Anne Adam, Ria Knittel and Gabi Frommer-Kästle are thanked for their skilful technical assistance. Financial support by the Deutsche Krebshilfe—Mildred Scheel-Stiftung to HW and SN (grants 107686 and 109219) is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Neurosurgery, University of Tübingen, Tübingen, Germany

    Susan Noell, Rainer Ritz & Marcos Tatagiba

  2. Department of Pathology, Institute of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany

    Karen Wolburg-Buchholz, Hartwig Wolburg & Petra Fallier-Becker

  3. Institute of Anatomy, University of Tübingen, Tübingen, Germany

    Andreas F. Mack

  4. Department of Neuropathology, Institute of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany

    Rudi Beschorner

  5. Institute of Pathology and Neuropathology, Liebermeisterstraße 8, 72076, Tübingen, Germany

    Hartwig Wolburg

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  1. Susan Noell
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  2. Karen Wolburg-Buchholz
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  8. Petra Fallier-Becker
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Correspondence to Hartwig Wolburg.

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This work is dedicated to Prof. Dr. Wolfgang Schlote, the former academic mentor of H.W., on the occasion of his 80th birthday.

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Noell, S., Wolburg-Buchholz, K., Mack, A.F. et al. Dynamics of expression patterns of AQP4, dystroglycan, agrin and matrix metalloproteinases in human glioblastoma. Cell Tissue Res 347, 429–441 (2012). https://doi.org/10.1007/s00441-011-1321-4

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