Cancer Therapy: Preclinical The Integrin Inhibitor Cilengitide Affects Meningioma Cell Motility and Invasion

Purpose: Meningiomas are frequent intracranial or spinal neoplasms, which recur frequently and can show aggressive clinical behaviour. We elucidated the impact of the integrin inhibitor cilengitide on migration, proliferation, and radiosensitization of meningioma cells. Experimental Design: We analyzed integrin expression in tissue microarrays of human meningiomas and the antimeningioma properties of cilengitide in cell cultures, subcutaneous and intracranial nude mouse models by measuring tumor volumes and survival times. Results: avb5 was the predominantly expressed integrin heterodimer in meningiomas, whereas avb3 was mainly detected in tumor blood vessels. Application of up to 100 mg/mL cilengitide resulted in only mildly reduced proliferation/survival ofmeningioma cell lines. Effects on cell survival could be enhancedby irradiation. One mg/mL cilengitide was sufficient to significantly inhibit meningioma cell migration and invasion in vitro. A daily dosageof 75mg/kgdidneither affect tumor volumesnoroverall survival (P1⁄40.813, log-rank test), but suppressed brain invasion in a significant fractionof treated animals. A combination of 75 mg/kg cilengitide daily and irradiation (2 5 Gy) led to a 67% reduction of MRI-estimated tumor volumes in the intracranial model (P < 0.01), whereas the corresponding reduction reached by irradiation alone was only 55% (P < 0.05). Conclusions: These data show that a monotherapy with cilengitide is not likely to achieve major responses in rapidly growingmalignant meningiomas, although brain invasionmay be reduced because of the strong antimigratory properties of the drug. The combination with radiotherapy warrants further attention. Clin Cancer Res; 19(19); 1–11. 2013 AACR.