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GSE81964
Mus musculus
30 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Medulloblastoma (MB), a tumor of the cerebellum, is the most common malignant brain tumor in children. One third of all human MB exhibits a gene expression signature of Sonic hedgehog (Shh) signaling. Hedgehog (Hh) pathway inhibitors have shown efficacy in clinical trials for MB, however, tumors develop resistance to these compounds, highlighting the need to identify additional therapeutic targets for treatment. We have identified a role for Norrin signaling in tumor initiation in the Patched (Ptch) mouse model of MB. Norrin is a secreted factor that functions as an atypical Wnt by binding to the Frizzled4 (Fzd4) receptor on endothelial cells to activate canonical beta-catenin-mediated Wnt signaling pathway. In the cerebellum, activation of Norrin/Fzd4 signaling is required for the establishment and maintenance of the blood brain barrier (BBB). We have identified a role for Norrin signaling in the stroma as a potent tumor inhibitory signal. Inactivation of Norrin in Ptch+/- mice significantly shortens latency and increases MB incidence. This phenotype is associated with an increased frequency of pre-tumor lesions and their conversion to malignancy. In this context, loss of Norrin signalling in endothelial cells is associated with an accelerated transition to a pro-tumor stroma characterized by vascular permeability, inflammation and angiogenic remodelling. Accordingly, loss of Ndp significantly alters the stromal gene expression signature of established Ptch MB.
Publication Title
Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Medulloblastoma (MB), a tumor of the cerebellum, is the most common malignant brain tumor in children. One third of all human MB exhibits a gene expression signature of Sonic hedgehog (Shh) signaling. Hedgehog (Hh) pathway inhibitors have shown efficacy in clinical trials for MB, however, tumors develop resistance to these compounds, highlighting the need to identify additional therapeutic targets for treatment. We have identified a role for Norrin signaling in tumor initiation in the Patched (Ptch) mouse model of MB. Norrin is a secreted factor that functions as an atypical Wnt by binding to the Frizzled4 (Fzd4) receptor on endothelial cells to activate canonical beta-catenin-mediated Wnt signaling pathway. In the cerebellum, activation of Norrin/Fzd4 signaling is required for the establishment and maintenance of the blood brain barrier (BBB). We have identified a role for Norrin signaling in the stroma as a potent tumor inhibitory signal. Inactivation of Norrin in Ptch+/- mice significantly shortens latency and increases MB incidence. This phenotype is associated with an increased frequency of pre-tumor lesions and their conversion to malignancy. In this context, loss of Norrin signalling in endothelial cells is associated with an accelerated transition to a pro-tumor stroma characterized by vascular permeability, inflammation and angiogenic remodelling. Accordingly, loss of Ndp significantly alters the stromal gene expression signature of established Ptch MB.
Publication Title
Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation.
Sample Metadata Fields
Specimen part
View Samples