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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 09, 2014 |
| Title |
TMPRSS2 Influences Prostate Cancer Metastasis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
TMPRSS2 is an androgen-regulated cell surface serine protease expressed predominantly in prostate epithelium. TMPRSS2 is expressed highly in localized high-grade prostate cancers and in the majority of human prostate cancer metastasis. Through the generation of mouse models with a targeted deletion of Tmprss2, we demonstrate that the activity of this protease regulates cancer cell invasion and metastasis to distant organs. By screening combinatorial peptide libraries we identified a spectrum of TMPRSS2 substrates that include pro-hepatocyte growth factor (HGF). HGF activated by TMPRSS2 promoted c-Met receptor tyrosine kinase signaling, and initiated a pro-invasive EMT phenotype. Chemical library screens identified a potent bioavailable TMPRSS2 inhibitor that suppressed prostate cancer metastasis in vivo. Together, these findings provide a mechanistic link between androgen-regulated signaling programs and prostate cancer metastasis that operate via context-dependent interactions with extracellular constituents of the tumor microenvironment.
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| Overall design |
Custom mouse cDNA microarrays were used to measure transcript levels in microdissected anterior prostate tumors from Tmprss2+/+;TRAMP mice, Tmprss2-/-;TRAMP mice or strain-matched benign epithelium. All samples were laser-capture microdissected and total RNA isolated and amplified prior to hybridization against a reference pool of normal adult mouse tissues.
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| Contributor(s) |
Lucas JM, Heinlein C, Kim T, Hernandez SA, Malik MS, True LD, Morrissey C, Corey E, Montgomery B, Mostaghel E, Clegg N, Coleman I, Brown CM, Schneider EL, Craik C, Simon J, Bedalov T, Nelson PS |
| Citation(s) |
25122198 |
| Submission date |
Jun 25, 2014 |
| Last update date |
Sep 11, 2014 |
| Contact name |
Ilsa Coleman |
| E-mail(s) |
icoleman@fredhutch.org
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| Phone |
206-667-1703
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| Organization name |
Fred Hutchinson Cancer Center
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| Department |
Human Biology
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| Lab |
Peter Nelson
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| Street address |
1100 Fairview Ave N, E2-112
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98109 |
| Country |
USA |
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| Platforms (1) |
| GPL4070 |
Mouse Prostate MPEDB cDNA Array v2 |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA253587 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE58822_RAW.tar |
12.6 Mb |
(http)(custom) |
TAR (of GPR) |
| Processed data included within Sample table |
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