Expression of hypoxia-inducible carbonic anhydrases in brain tumors

Proescholdt, Martin A. and Mayer, Christina and Kubitza, Marion and Schubert, Thomas and Liao, S. Y. and Stanbridge, E. J. and Ivanov, S. V. and Oldfield, E. H. and Brawanski, Alexander and Merrill, M. J. (2005) Expression of hypoxia-inducible carbonic anhydrases in brain tumors. NEURO-ONCOLOGY, 7 (4). pp. 465-475. ISSN 1522-8517, 1523-5866

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Abstract

Malignant brain tumors exhibit distinct metabolic characteristics. Despite high levels of lactate, the intracellular pH of brain tumors is more alkaline than normal brain. Additionally, with increasing malignancy, brain tumors display intratumoral hypoxia. Carbonic anhydrase (CA) IX and XII are transmembrane isoenzymes that are induced by tissue hypoxia. They participate in regulation of pH homeostasis by catalyzing the reversible hydration of carbon dioxide. The aim of our study was to investigate whether brain tumors of different histology and grade of malignancy express elevated levels of CA IX and XII as compared to normal brain. We analyzed 120 tissue specimens from brain tumors (primary and metastatic) and normal brain for CA IX and XII expression by immunohistochemistry, Western blot, and in situ hybridization. Whereas normal brain tissue showed minimal levels of CA IX and XII expression, expression in tumors was found to be upregulated with increased level of malignancy. Hemangioblastomas, from patients with von Hippel-Lindau disease, also displayed high levels of CA IX and XII expression. Comparison of CA IX and XII staining with HIF-let staining revealed a similar microanatomical distribution, indicating hypoxia as a major, but not the only, induction factor. The extent of CA IX and XII staining correlated with cell proliferation, as indicated by Ki67 labeling. The results demonstrate that CA IX and XII are upregulated in intrinsic and metastatic brain tumors as compared to normal brain tissue. This may contribute to the management of tumor-specific acid load and provide a therapeutic target.

Item Type: Article
Uncontrolled Keywords: POSITRON EMISSION TOMOGRAPHY; MN/CA IX; DIAGNOSTIC BIOMARKER; INVIVO MEASUREMENT; CELL CARCINOMA; TYROSINE PHOSPHATASE; OXYGEN-TENSION; REGIONAL BRAIN; HUMAN GLIOMAS; RAT-BRAIN; pH regulation; carbonic anhydrase; glioma; hypoxia
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Neurochirurgie
Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 26 Apr 2021 12:26
Last Modified: 26 Apr 2021 12:26
URI: https://pred.uni-regensburg.de/id/eprint/35607

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