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An α5β1 integrin inhibitor attenuates glioma growth

Item Type:Article
Title:An α5β1 integrin inhibitor attenuates glioma growth
Creators Name:Faerber, K. and Synowitz, M. and Zahn, G. and Vossmeyer, D. and Stragies, R. and van Rooijen, N. and Kettenmann, H.
Abstract:Integrins are heterodimeric transmembrane proteins, which mediate cell-cell and cell-extracellular matrix (ECM) interaction. We show, that an inhibitor of alpha5 beta1 integrin ({alpha}5{beta}1), JSM6427, attenuated glioma growth and decreased the density of microglia at the tumor border. 21 days after glioma cell injection into an experimental mouse model, the tumor volume was significantly smaller after treating animals for 14 days with JSM6427 as compared to controls. We could demonstrate the expression of integrin {alpha}5 beta1 on both microglia and glioma cells using flow cytometry. In a slice culture we could compare glioma growth in the presence and absence of microglia. Slices injected with glioma cells were treated with the integrin inhibitor JSM6427 and showed a significant reduction in tumor size as compared to control. Depleting microglial cells from the slice culture by treatment with clodronate liposomes abrogated the effect of JSM6427 on glioma invasion indicating that the presence of microglia is required. We show further, that microglial migration, and proliferation was attenuated dose-dependently by JSM6427.
Keywords:Microglia, alpha5beta1 Integrin, Proliferation, Migration, Glioma, Aminopyridines, Cell Movement, Cultured Cells, Cytokines, Integrin alpha5beta1, Inbred C57BL Mice, Neoplasm Transplantation, Propionic Acids, Tissue Culture Techniques, Animals, Mice
Source:Molecular and Cellular Neuroscience
Publisher:Academic Press
Page Range:579-585
Date:November 2008
Official Publication:https://doi.org/10.1016/j.mcn.2008.08.005
PubMed:View item in PubMed

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