Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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

ABSTRACT: 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).

ORGANISM(S): Mus musculus

SUBMITTER: Ulrike Nuber

PROVIDER: E-GEOD-37671 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The endometrium contains a distinct population of immune cells consisting of 70% natural killer (NK) cells that undergo cyclic changes during the menstrual cycle. However, how these uterine NK (uNK) cells interact with uterine stromal cells (SC) remains unclear. We therefore investigated the paracrine effect of medium conditioned by uNK cells on the gene expression profile of endometrial SC in-vitro using a cDNA Microarray. Our results, verified by real-time PCR and ELISA, reveal that soluble factors from uNK cells substantially alter endometrial SC gene expression. The largest group of up-regulated genes found were chemokines and cytokines, including IL-15 and IL-15RÎ±. The latter could produce a niche for uNK cells allowing proliferation within and recruitment into the uterus, as seen in bone marrow. In addition, the most abundantly up-regulated genes, including IL-8, CCL8 and CXCL1 have also been shown to be stimulated by contact of SC with trophoblast, suggesting that uNK cells work synergistically to support the initial trophoblast migration during implantation. Overall this study demonstrates for the first time the paracrine communication between uNK cells and uterine SC, and adds to the understanding of how the uterine immune system contributes to the changes seen within the cycling endometrium. Keywords: Response of endometrial stromal cells to uNK conditioned medium This study was designed to identify the response of non-decidualised stromal cells from the endometrium, to soluble factors secreted by uterine NK cells. Endometrial stromal cells were isolated from 7 patients and treated with control medium or medium conditioned by uterine Nk cells. THE 'REF' COLUMN ON EACH ARRAY IS THE SIGNAL PRODUCED BY A COMMON REFERNCE RNA SAMPLE THAT WAS LABELLED AS A SINGLE BATCH SAMPLE AND HYBRIDISED TO ALL THE ARRAYS- IT IS A 'COMMON REFERENCE'. THE 'TEST' SAMPLE COMPRISES EACH INDIVIDUAL SAMPLE OF CELLS TREATED AS DESCRIBED IN THE SERIES SUBMISSION. FOR EXAMPLE; SAMPLE Y1 (gsm2435820) IS RNA FROM PATIENT 1 TREATED WITH CONTROL MEDIUM, SAMPLE G1 (GSM245371) IS RNA FROM PATIENT 1 TREATED WITH NK CONDITIONED MEDIUM THESE TWO SAMPLES THEREFORE FORM A PAIR- IE CELLS FROM THE SAME PATIENT TREATED WITH CONTROL OR NK-CONDITIONED MIDIUM. Y2,G2 ARE FROM PATIENT 2, ETC

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

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