A1 adenosine receptors in microglia control glioblastoma-host interaction.
We report that experimental glioblastoma grow more vigorously in A(1) adenosine receptor (A(1)AR)-deficient mice associated with a strong accumulation of microglial cells at and around the tumors. A(1)ARs were prominently expressed in microglia associated with tumor cells as revealed with immunocytochemistry but low in microglia in the unaffected brain tissue. The A(1)AR could also be detected on microglia from human glioblastoma resections. To study functional interactions between tumor and host cells, we studied glioblastoma growth in organotypical brain slice cultures. A(1)AR agonists suppressed tumor growth. When, however, microglial cells were depleted from the slices, the agonists even stimulated tumor growth. Thus, adenosine attenuates glioblastoma growth acting via A(1)AR in microglia.
Synowitz
Michael
M
Cellular Neuroscience Group, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Glass
Rainer
R
Färber
Katrin
K
Markovic
Darko
D
Kronenberg
Golo
G
Herrmann
Ken
K
Schnermann
Juergen
J
Nolte
Christiane
C
van Rooijen
Nico
N
Kiwit
Juergen
J
Kettenmann
Helmut
H
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division; D002478:Cells, Cultured; D017930:Genes, Reporter; D005838:Genotype; D005909:Glioblastoma / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology* / Q000502:physiology; D043682:Receptor, Adenosine A1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D043682:Receptor, Adenosine A1; D000241:Adenosine