engleski

Imaging bone morphogenetic protein 7 induced cell cycle arrest in experimental gliomas

Bone morphogenetic protein 7 (BMP-7) belongs to the superfamily of TGF-β-like cytokines, which can either act as tumor suppressors or as tumor promoters depending on cell type and differentiation. Our investigations focused on analyzing effects of BMP-7 during glioma cell proliferation in vitro and in vivo. BMP-7 treatment decreased the proliferation of Gli36ΔEGFR-LITG glioma cells up to 50% via a cell cycle arrest in the G1 phase but not by induction of apoptosis. This effect was mediated by the modulation of the expression and phosphorylation of cyclin dependent kinase 2, cyclin dependent kinase inhibitors p21 and downstream retinoblastoma protein. Furthermore, in vivo optical imaging of luciferase activity (LUC-OI) of Gli36ΔEGFR-LITG cells implanted intracranially into nude mice in the presence or absence of BMP-7 treatment corroborated the anti-proliferative effects of this cytokine. This report clearly underlines the tumor suppressive role of BMP-7 in glioma-derived cells. Taken together our results indicate that manipulating the BMP/TGF-β signaling cascade may serve as a new strategy for imaging- guided molecular-targeted therapy of malignant gliomas.

BMP7 ; glioma ; tumor suppression

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