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Status |
Public on Apr 03, 2014 |
Title |
Pten null prostate epithelium promotes localized myeloid-derived suppressor cell expansion and immune suppression during tumor initiation and progression [cell lines] |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Chronic inflammation is known to associate with prostate cancer development, but how epithelium-associated cancer initiating events cross-talk to inflammatory cells during prostate cancer initiation and progression is largely unknown. Using the Pten null murine prostate cancer model, we show an expansion of Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs) occurring intra-prostatically immediately following epithelium-specific Pten deletion without expansion in hematopoietic tissues. This MDSC expansion is accompanied by sustained immune suppression. Prostatic Gr-1+CD11b+ cells, but not those isolated from the spleen of the same tumor bearing mice, suppress T cell proliferation and express high levels of Arginase 1 and iNOS. Mechanistically, loss of PTEN in the epithelium leads to a significant upregulation of genes within the inflammatory response and cytokine-cytokine receptor interaction pathways, including Csf-1 and IL-1β, two genes known to induce MDSC expansion and immunosuppressive activities. Treating Pten null mice with the selective CSF-1 receptor inhibitor GW2580 decreases MDSC infiltration and relieves the associated immunosuppressive phenotype. Our study indicates that epithelium-associated tumor initiating events trigger the secretion of inflammatory cytokines and promote localized MDSC expansion and immune suppression, thereby promoting tumor progression
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Overall design |
Custom Agilent 4x44K whole mouse genome expression oligonucleotide microarrays were used to measure transcript levels in murine Pten null prostate cancer cell lines. Benign mouse prostate epithelia as wild type control against cell lines. Each cohort had three biological replicates.
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Contributor(s) |
Garcia AJ, Ruscetti M, Arenzana TL, Tran LM, Bianchi-Frias D, Sybert E, Priceman SJ, Wu L, Nelson PS, Smale ST, Wu H |
Citation(s) |
24662052 |
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Submission date |
Apr 02, 2014 |
Last update date |
Sep 09, 2014 |
Contact name |
Linh My Tran |
E-mail(s) |
linhtran@ucla.edu
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Organization name |
University of Los Angeles
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Department |
Medicine - Pulmonary & Critical Care
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Lab |
Dubinett Lab
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Street address |
Box 951690, 37-131 CHS
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City |
Los Angeles |
State/province |
California |
ZIP/Postal code |
90095-1690 |
Country |
USA |
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Platforms (1) |
GPL10361 |
Agilent-016579 Nelson Whole Mouse Genome Microarray 4x44K |
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Samples (15)
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GSM1361953 |
Benign Prostate Epithelial Cell Replicate 1 |
GSM1361954 |
Benign Prostate Epithelial Cell Replicate 2 |
GSM1361955 |
Benign Prostate Epithelial Cell Replicate 3 |
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This SubSeries is part of SuperSeries: |
GSE56470 |
Pten null prostate epithelium promotes localized myeloid-derived suppressor cell expansion and immune suppression during tumor initiation and progression |
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Relations |
BioProject |
PRJNA243378 |