Artikel
The role of the fatty acid synthase in meningiomas of different WHO-grading
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Autoren
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C. Ewald
- Klinik für Neurochirurgie, Friedrich Schiller Universität, Jena
| Veröffentlicht: | 20. Mai 2009 |
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Gliederung
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Objective: Fatty acid synthase (FAS) is known to be expressed in some human cancers including breast and prostate cancer. Increased FAS expression has been related to aggressive biological behaviour. FAS expression has been also associated with steroid metabolism. Up to now the role of FAS in human meningiomas has not been determined yet. FAS expression was studied in human meningiomas in correlation to histological grading. FAS expression as well as the effects of FAS inhibition was also determined in meningioma cell lines derived from benign and malignant meningiomas, respectively.
Methods: FAS immunoexpression was determined using a tissue microarray slide containing 39 meningiomas (20 WHO grade I, 11 WHO grade II, 7 WHO grade III). Real-time PCR measurement of FAS mRNA levels was done in 15 tumor samples (9 grade I, 4 grade II, and 2 grade III tumors) and five cell lines. To define the effects of FAS inhibition onto the biological behaviour of the tumour cells two cell lines with strong expression were treated with the specific inhibitors Cerulenin and C75. The results were determined by an MTT- and a proliferation assay.
Results: Immunoexpression of FAS was found in 10/20 grade I, 9/11 grade II, and 7/7 grade III tumors, respectively. All grade I-tumors showed only weak to moderate staining, while most aggressive meningiomas were strongly immunopositive for FAS. mRNA levels were five-fold higher in grade II and grade III tumors compared to grade I meningiomas. In line with this finding, three cell lines derived from malignant meningiomas also contained higher FAS mRNA levels than the two lines derived from benign meningiomas. Inhibition of FAS in one benign and one malignant cell line was followed by the death of more than 50% of the cells and significantly reduced cell proliferation especially in the anaplastic cell line after incubation with Cerulenin
Conclusions: FAS expression is strongly increased in aggressive meningiomas and might significantly contribute to the biology of these tumors. Inhibition leads to cell death so that we found a possible new target for anti-tumor therapy, especially in high grade meningiomas and in cases where surgery and radiation have failed.
