Mouse high grade astrocytoma cells (GL261) treated with neural stem/precursor cell (NPC) conditioned medium or non-conditioned medium (control)

Primary astrocytomas of high histopathological grade (HG-astrocytomas) are largely restricted to older patients and are almost invariably fatal despite multimodal therapy. Here, we show that the young brain has an endogenous defense mechanisms against HG-astrocytomas. Neural precursor cells (NPCs) migrate to HG-astrocytomas, reduce glioma expansion and prolong survival by releasing a group of fatty-acid ethanolamides that have agonistic activity on the vanilloid receptor (transient receptor potential vanilloid subfamily member-1; TRPV1). TRPV1 expression is much higher in HG-astrocytomas than in the tumor-free brain and TRPV1 stimulation triggers tumor cell-death via the activating transcription factor-3 (ATF3) controlled branch of the ER-stress pathway. The anti-tumourigenic response of NPCs is lost with aging. NPC-mediated tumor suppression can be mimicked in the old brain by systemic administration of the synthetic vanilloid Arvanil, indicating that TRPV1 agonists hold potential as new HG-astrocytoma therapeutics. The goal of this microarray study was understand how neural stem / precursor cell (NPC) induced high grade astrocytoma cell-death is controlled by changes in gene expression. We investigated the gene-expression pattern in mouse high grade astrocytoma GL261 cells after incubation with NPC non-conditioned medium (controls) or NPC-conditioned medium by microarrays and found that endoplasmic reticulum stress genes like the activating transcription factor-3 (ATF3) were robustly up-regulated in NPC-conditioned medium treated mouse high grade astrocytoma cells, compared to controls. Comparison of two experimental groups (conditioned medium treated versus non-conditioned medium treated) in three dye swap experiments (6 arrays used in total).