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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.

ORGANISM(S): Mus musculus

PROVIDER: GSE37671 | GEO | 2012/05/01

SECONDARY ACCESSION(S): PRJNA162653

REPOSITORIES: GEO

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

Project description: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).

2012-04-30 | E-GEOD-37671 | biostudies-arrayexpress

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SUMOylation-Induced Membrane Localization of TRPV1 Suppresses Proliferation and Migration in Gastric Cancer Cells

Project description:Gastric cancer (GC) remains a significant health challenge due to its high mortality rate and the limited efficacy of current targeted therapies. A critical barrier in developing more effective treatments is the lack of understanding of specific mechanisms driving GC progression. This study investigates the role of Transient Receptor Potential Vanilloid 1 (TRPV1), a non-selective cation channel known for its high Ca2+ permeability and tumor-suppressive properties in gastrointestinal cancers. Specifically, we explore the impact of SUMOylation—a dynamic and reversible post-translational modification—on TRPV1's function in GC. We demonstrate that SUMOylation of TRPV1 inhibits cell proliferation and migration in MGC-803 and AGS gastric cancer cells. By mutating amino acids near TRPV1's existing SUMO motif (slKpE), we created a bidirectional SUMO motif (EψKψE) that enhances TRPV1 SUMOylation, resulting in further suppression of GC cell proliferation and migration. In vivo studies support these findings, showing that TRPV1 SUMOylation prevents spontaneous tumorigenesis in a mouse gastric cancer model. Further investigation reveals that TRPV1 SUMOylation increases the protein's membrane expression by inhibiting its interaction with the adaptor-related protein complex 2 mu 1 subunit (AP2M1). This elevated membrane expression leads to increased intracellular Ca2+ influx, activating the AMP-activated protein kinase (AMPK) pathway, which in turn inhibits the proliferation and migration of GC cells. In conclusion, our study elucidates a novel mechanism wherein TRPV1 SUMOylation promotes its membrane expression and activates the TRPV1-Ca2+-AMPK signaling pathway, thereby inhibiting GC cell proliferation and migration. These findings enhance our understanding of the molecular dynamics in gastric cancer and could provide a new theoretical basis for clinical treatment strategies.

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Hierarchical synergy of Pten, p53 and Rb pathways in high-grade astrocytoma induced in adult brain

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2011-03-23 | E-GEOD-22927 | biostudies-arrayexpress

Nanoparticles-mediated TRPV1 channel blockade amplifies cancer thermo-immunotherapy via heat shock factor 1 modulation

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