A sub(1) Adenosine Receptors in Microglia Control Glioblastoma-Host Interaction

We report that experimental glioblastoma grow more vigorously in A sub(1) adenosine receptor (A sub(1)AR)-deficient mice associated with a strong accumulation of microglial cells at and around the tumors. A sub(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 sub(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 sub(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 sub(1)AR in microglia. (Cancer Res 2006; 66(17): 8550-7)