Effect of the integrin inhibitor cilengitide on TGF-beta signaling.

2055 Background: Glioblastoma is the most malignant form of intrinsic brain tumors. One of its characteristic features, angiogenesis, is mediated by the expression of integrins αvβ3 and αvβ5 on tumor-associated vasculature. Cilengitide is a synthetic peptide which inhibits ligand binding to the αvβ3 and αvβ5 integrins. The addition of cilengitide to the standard treatment regimen of radiochemotherapy in patients with newly diagnosed glioblastoma demonstrated promising results without significant toxicity which led to the initiation of a randomized phase registration III trial. Besides other functions, av-integrins can be involved in the activation of the cytokine transforming growth factor (TGF)-β which contributes to the malignant phenotype of glioma cells. Methods: Integrin expression was examined by immunohistochemistry and flow cytometry. The effects of cilengitide on TGF-β signaling in glioma cells were investigated by PCR, immunoblot and ELISA. Further assessments included reporter assays and glioma...