TY - JOUR
T1 - Fatty acid synthase as a novel target for meningioma therapy
AU - Haase, Daniela
AU - Schmidl, Stefan
AU - Ewald, Christian
AU - Kalff, Rolf
AU - Huebner, Christian
AU - Firsching, Raimund
AU - Keilhoff, Gerburg
AU - Evert, Matthias
AU - Paulus, Werner
AU - Gutmann, David H.
AU - Lal, Anita
AU - Mawrin, Christian
PY - 2010/8
Y1 - 2010/8
N2 - High levels of fatty acid synthase (FAS) expression have been reported in hormone receptor-positive tumors, including prostate, breast, and ovarian cancers, and its inhibition reduces tumor growth in vitro and in vivo. Similar to other hormone receptor-positive tumor types, meningiomas are progesterone receptor- and estrogen receptor-immunoreactive brain tumors. To define the role of FAS in human meningioma growth control, we first analyzed the FAS expression using a tissue microarray containing 38 meningiomas and showed increased FAS expression in 70% of atypical WHO grade II and anaplastic WHO grade III meningiomas compared with 10% of benign WHO grade I tumors. We next confirmed this finding by real-time PCR and Western blotting. Second, we demonstrated that treatment with the FAS inhibitor, cerulenin (Cer), significantly decreased meningioma cell survival in vitro. Third, we showed that Cer treatment reduced FAS expression by modulating Akt phosphorylation (activation). Fourth, we demonstrated that Cer treatment of mice bearing meningioma xenografts resulted in significantly reduced tumor volumes associated with increased meningioma cell death. Collectively, our data suggest that the increased FAS expression in human meningiomas represents a novel therapeutic target for the treatment of unresectable or malignant meningioma.
AB - High levels of fatty acid synthase (FAS) expression have been reported in hormone receptor-positive tumors, including prostate, breast, and ovarian cancers, and its inhibition reduces tumor growth in vitro and in vivo. Similar to other hormone receptor-positive tumor types, meningiomas are progesterone receptor- and estrogen receptor-immunoreactive brain tumors. To define the role of FAS in human meningioma growth control, we first analyzed the FAS expression using a tissue microarray containing 38 meningiomas and showed increased FAS expression in 70% of atypical WHO grade II and anaplastic WHO grade III meningiomas compared with 10% of benign WHO grade I tumors. We next confirmed this finding by real-time PCR and Western blotting. Second, we demonstrated that treatment with the FAS inhibitor, cerulenin (Cer), significantly decreased meningioma cell survival in vitro. Third, we showed that Cer treatment reduced FAS expression by modulating Akt phosphorylation (activation). Fourth, we demonstrated that Cer treatment of mice bearing meningioma xenografts resulted in significantly reduced tumor volumes associated with increased meningioma cell death. Collectively, our data suggest that the increased FAS expression in human meningiomas represents a novel therapeutic target for the treatment of unresectable or malignant meningioma.
KW - Fatty acid synthase
KW - Meningioma
KW - Therapy
UR - http://www.scopus.com/inward/record.url?scp=78149474133&partnerID=8YFLogxK
U2 - 10.1093/neuonc/noq004
DO - 10.1093/neuonc/noq004
M3 - Article
C2 - 20511185
AN - SCOPUS:78149474133
SN - 1522-8517
VL - 12
SP - 844
EP - 854
JO - Neuro-oncology
JF - Neuro-oncology
IS - 8
ER -