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Distinct patterns of hypoxic expression of carbonic anhydrase IX (CA IX) in human malignant glioma cell lines

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Abstract

The hypoxia-inducible enzyme carbonic anhydrase IX (CA IX) has recently been discussed as a surrogate marker of tumor hypoxia, an indicator of prognosis and a potential therapeutic target in malignant glioma. To characterize patterns of expression of CA IX in human malignant glioma cells, we studied CA IX protein, CA9 mRNA and hypoxia-inducible factor-1α (HIF-1α) protein levels in U87-MG, U251, U373 and GaMG cells exposed to in vitro hypoxia (1, 6 or 24 h at 5%, 1% or 0.1% O2). All cell lines displayed a strong hypoxic induction of CA9 mRNA in response to prolonged severe hypoxia with cell-line specific patterns at moderate to mild hypoxia and shorter treatment times. Only U87-MG exhibited a strong constitutive, normoxic expression of CA IX protein without a detectable change under hypoxia. In U251 and GaMG cell lines, a marked induction of CA IX protein in response to severe hypoxia was seen. CA IX changes under severe hypoxia and the inhibitory effect of the glycolysis inhibitor iodoacetate (IAA, 50 µM) on hypoxic CA IX overexpression were paralleled by the results for HIF-1α protein. Therefore, immunohistochemical CA IX staining in human malignant glioma specimens can result from low oxygen concentrations or constitutive, oncogene-related, overexpression both of which may be prognostically relevant.

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Acknowledgements

This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft (to DV) and by IZKF Wuerzburg (to CH and GHV). We thank Prof. Dr. Ulf Rapp, MSZ Institute, University of Würzburg, for the possibility to use the radioactivity laboratories and Bayer Healthcare Co. for provision of the M75 monoclonal antibody.

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Wuerzburg, Josef-Schneider-Str. 11, 97080, Wuerzburg, Germany

    Harun M. Said, Adrian Staab, Astrid Katzer, Michael Flentje & Dirk Vordermark

  2. Department of Neurosurgery, University of Wuerzburg, Wuerzburg, Germany

    Carsten Hagemann & Giles H. Vince

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  1. Harun M. Said
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Correspondence to Harun M. Said.

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Said, H.M., Staab, A., Hagemann, C. et al. Distinct patterns of hypoxic expression of carbonic anhydrase IX (CA IX) in human malignant glioma cell lines. J Neurooncol 81, 27–38 (2007). https://doi.org/10.1007/s11060-006-9205-2

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  • DOI: https://doi.org/10.1007/s11060-006-9205-2

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