Document Detail

An alpha5beta1 integrin inhibitor attenuates glioma growth.
MedLine Citation:
PMID:  18804537     Owner:  NLM     Status:  MEDLINE    
Integrins are heterodimeric transmembrane proteins, which mediate cell-cell and cell-extracellular matrix (ECM) interaction. We show, that an inhibitor of alpha5 beta1 integrin (alpha5beta1), 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 alpha5beta1 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.
Katrin Färber; Michael Synowitz; Grit Zahn; Dörte Vossmeyer; Roland Stragies; Nico van Rooijen; Helmut Kettenmann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-09-04
Journal Detail:
Title:  Molecular and cellular neurosciences     Volume:  39     ISSN:  1095-9327     ISO Abbreviation:  Mol. Cell. Neurosci.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-25     Completed Date:  2009-01-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9100095     Medline TA:  Mol Cell Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  579-85     Citation Subset:  IM    
Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strabetae 10, D-13125 Berlin, Germany.
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MeSH Terms
Aminopyridines / metabolism
Cell Movement / physiology
Cells, Cultured
Cytokines / secretion
Glioma* / metabolism,  pathology
Integrin alpha5beta1 / antagonists & inhibitors*,  metabolism
Mice, Inbred C57BL
Microglia / cytology,  metabolism
Neoplasm Transplantation
Propionic Acids / metabolism
Tissue Culture Techniques
Reg. No./Substance:
0/Aminopyridines; 0/Cytokines; 0/Integrin alpha5beta1; 0/Propionic Acids

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