Proescholdt, Martin A. and Merrill, Marsha J. and Stoerr, Eva-Maria and Lohmeier, Annette and Pohl, Fabian and Brawanski, Alexander (2012) Function of carbonic anhydrase IX in glioblastoma multiforme. NEURO-ONCOLOGY, 14 (11). pp. 1357-1366. ISSN 1522-8517, 1523-5866
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-CELL GROWTH; BRAIN-TUMORS; CA-IX; EXTRACELLULAR PH; POOR-PROGNOSIS; GLIOMA-CELLS; IN-VIVO; HYPOXIA; EXPRESSION; SURVIVAL; apoptosis; CAIX; hypoxia; invasion; pH |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurochirurgie Medicine > Lehrstuhl für Strahlentherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 May 2020 10:58 |
| Last Modified: | 04 May 2020 10:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17892 |
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