| Item type: | Article | ||||||||||||||||||||||||||||||||||
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| Journal or Publication Title: | Neuro-oncology | ||||||||||||||||||||||||||||||||||
| Publisher: | Oxford Univ. Press | ||||||||||||||||||||||||||||||||||
| Volume: | 14 | ||||||||||||||||||||||||||||||||||
| Number of Issue or Book Chapter: | 11 | ||||||||||||||||||||||||||||||||||
| Page Range: | pp. 1357-1366 | ||||||||||||||||||||||||||||||||||
| Date: | 2012 | ||||||||||||||||||||||||||||||||||
| Institutions: | Medicine > Zentren des Universitätsklinikums Regensburg > Zentrum für Hirntumore (ZHT) | ||||||||||||||||||||||||||||||||||
| Identification Number: |
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| Classification: |
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| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||||||||||||||||||||||||||||||||
| Status: | Published | ||||||||||||||||||||||||||||||||||
| Refereed: | Yes, this version has been refereed | ||||||||||||||||||||||||||||||||||
| Created at the University of Regensburg: | Unknown | ||||||||||||||||||||||||||||||||||
| Item ID: | 29172 |
Abstract
Carbonic anhydrase (CA) IX is over-expressed in glioblastoma; however, its functions in this context are unknown. Metabolically, glioblastomas are highly glycolytic, leading to a significant lactic acid load. Paradoxically, the intracellular pH is alkaline. We hypothesized that CAIX contributes to the extrusion of hydrogen ions into the extracellular space, thereby moderating intra- and ...
Abstract
Carbonic anhydrase (CA) IX is over-expressed in glioblastoma; however, its functions in this context are unknown. Metabolically, glioblastomas are highly glycolytic, leading to a significant lactic acid load. Paradoxically, the intracellular pH is alkaline. We hypothesized that CAIX contributes to the extrusion of hydrogen ions into the extracellular space, thereby moderating intra- and extracellular pH and creating an environment conductive to enhanced invasion. We investigated the role of CAIX as a prognostic marker in patients with glioblastoma and its biological function in vitro. CAIX expression was analyzed in 59 patients with glioblastoma by immunohistochemistry. The expression levels were correlated to overall survival. In vitro, U251 and Ln 18 glioblastoma cells were incubated under hypoxia to induce CAIX expression, and RNA interference (RNAi) was used to examine the function of CAIX on cell attachment, invasion, intracellular energy transfer, and susceptibility to adjuvant treatment. High CAIX expression was identified as an independent factor for poor survival in patients with glioblastoma. In vitro, cell attachment and invasion were strongly reduced after knockdown of CAIX. Finally, the effects of radiation and chemotherapy were strongly augmented after CAIX interference and were accompanied by a higher rate of apoptotic cell death. CAIX is an independent prognostic factor for poor outcome in patients with glioblastoma. Cell attachment, invasion, and survival during adjuvant treatment are significantly influenced by high CAIX expression. These results indicate that inhibition of CAIX is a potential metabolic target for the treatment of patients with glioblastoma.
Metadata last modified: 29 Sep 2021 07:39
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