The influence of tamoxifen on the secretion of transforming growth factor-beta2 (TGF-beta2) in glioblastomas: in vitro and in vivo findings.
BACKGROUND
Only a minority of patients with malignant gliomas respond to continuous high-dose tamoxifen (TAM) treatment. Therefore a method to predict the efficiency of TAM-treatment would be desirable. Analogous to previous studies in breast cancer patients, we investigated whether the dynamics of TGF-beta2 plasma levels allow the prediction of response to TAM-treatment in glioblastoma patients as well.


METHODS
TGF-beta2 plasma levels of glioblastoma patients treated with 200 mg TAM/day on a continuous basis and of control patients not treated with TAM were measured by using an ELISA. In addition, the effect of TAM and 4-OH-TAM on the secretion of TGF-beta2 by established glioma cell lines as well as the effect of TGF-beta2 itself on cell proliferation were investigated in vitro.


RESULTS
The effect of TAM on TGF-beta2 plasma levels did not correlate with the clinical response to TAM-therapy in glioblastoma patients. The in vitro experiments showed that TAM and 4-OH-TAM stimulate established glioma cell lines to increase their secretion of TGF-beta2. Externally added TGF-beta2 (nM) had no effect on cell proliferation of the same cell lines.


CONCLUSIONS
In contrast to breast cancer patients, the clinical response to TAM in glioblastoma patients is not reflected by changes of TGF-beta2 plasma levels. It has to be assumed that, despite an increase of TGF-beta2 production by glioblastoma cells in response to TAM in vitro, such elevated production in vivo does not reach the plasma due to either the lower tumor burden in glioblastoma disease compared to breast cancer patients or due to some local sequestration process.
Puchner
Maximilian J A
MJ
Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany. PuchnerM@neurochirurgie.gilead.de
Köppen
Johannes A
JA
Zapf
Svenja
S
Knabbe
Cornelius
C
Westphal
Manfred
M
D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D002455:Cell Division / Q000187:drug effects; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005909:Glioblastoma / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000097:blood / Q000378:metabolism*; D053781:Transforming Growth Factor beta2; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D013629:Tamoxifen; C016601:afimoxifene; D003520:Cyclophosphamide