期刊
EXPERIMENTAL CELL RESEARCH
卷 337, 期 1, 页码 68-75出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2015.07.018
关键词
Integrin; Osteoclast; Metastatic bone disease; RGD-peptide
资金
- Independent research grant of Merck (Darmstadt) [FA711A0131]
- Austrian Science Fund (FWF) [P 23199] Funding Source: researchfish
Bone metastasis is a common burden in many types of cancer and has a severe impact on the quality of life in patients. Hence, specific therapeutic strategies inhibiting tumor induced osteolysis are urgently needed. In this study, we aimed to interfere with integrin adhesion receptors, which are central players of the bone resorption process. For this purpose, we used cilengitide, a cyclic RGD peptide, which blocks integrin alpha V beta 3 and alpha V beta 5-ligand binding. Our results revealed that cilengitide blocked osteodast maturation in a dose-dependent manner. In detail, pre-osteoclasts treated with cilengitide exhibited reduced cell spreading, cell migration and cell adhesion on RGD-containing matrix proteins, which are ligands of integrin alpha V. The activation of the most upstream signal transduction molecules of the integrin receptor-initiated pathway, FAK and c-Src, were consistently blocked by cilengitide. First evidence suggests that cilengitide might interfere with metastatic bone disease in vivo and this study describes a potential underlying mechanism of the inhibitory effect of cilengitide on alpha V-integrin expressing pre-osteoclasts by blocking integrin ligand binding and interfering with osteoclast maturation and cell behavior. In conclusion, our findings suggest that cilengitide, which interferes with alpha V-integrins on osteoclasts, may represent a novel therapeutic strategy in the treatment of malignant bone disease. (C) 2015 Elsevier Inc. All rights reserved.
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