An alpha5beta1 integrin inhibitor attenuates glioma growth.
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.
Färber
Katrin
K
Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strabetae 10, D-13125 Berlin, Germany. kettenmann@mdc-berlin.de
Synowitz
Michael
M
Zahn
Grit
G
Vossmeyer
Dörte
D
Stragies
Roland
R
van Rooijen
Nico
N
Kettenmann
Helmut
H
D000631:Aminopyridines / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D009368:Neoplasm Transplantation; D011422:Propionates / Q000378:metabolism; D046509:Tissue Culture Techniques
D000631:Aminopyridines; D016207:Cytokines; D039081:Integrin alpha5beta1; D011422:Propionates