In this renewal resubmission, we. propose to continue studies on prostate cancer (CaP) metastasis, especially focusing on the dissemination and growth of CaP in bone. This effort has coordinated much previous work from a variety of sources within the University of Washington (UW) milieu and is multidisciplinary, incorporating cancer and bone biology, cancer endocrinology, pathology and genomics. Institutional partners include the Fred Hutchinson Cancer Research Center and the UW Institute of Stem Cell Sciences. Inquiries into the mechanisms of CaP bone metastasis, are poorly studied, in part because of a lack of appropriate animal models and specimens. As the Progress Reports will demonstrate, these limitations have been largely overcome by our investigators, and the derived resources will enable the pursuit of the scientific objectives proposed. This P01 consists of 3 projects and 2 cores. Project 1 is entitled "The Detection, Isolation and Characterization of Disseminated Tumor Cells". This project will genomically characterize the DTC, looking at correlates to progression and biological function. It incorporates multiple studies exploring the stem cell aspects of DTC and the role of DTC in tumor dormancy. This is a new project, led by Dr. Robert Vessella that replaces the previous Project 1. Project 2 is entitled "Transmembrane Proteases and Prostate Carcinogenesis". This project, led by Dr. Pete Nelson, will focus heavily on the serine protease TMPRSS2 and the gene fusion TMPRSS2-ERG. Project 3 is entitled: "Determinants of Response to Type 1 Insulin-like Growth Factor Inhibition in Prostate Cancer". This project is led by Dr. Steve Plymate and is highly translational as it is focused on better understanding the role of IGF-1R as clinical trials at UW and elsewhere are being conducted to target this receptor. Projects 2 and 3 are continuations of very successful studies during the current funding period. Core A is the Biospecimen Core which acquires processes and distributes biospecimens. It also conducts pre-clinical xenograft studies and provides statistical support to the overall P01 program. Core B is the Administrative Core which provides overall administrative support to the investigators.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Special Emphasis Panel (ZCA1-RPRB-O (M1))
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Mohla, Suresh
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University of Washington
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Damodarasamy, Mamatha; Vernon, Robert B; Chan, Christina K et al. (2015) Hyaluronan in aged collagen matrix increases prostate epithelial cell proliferation. In Vitro Cell Dev Biol Anim 51:50-8
Long, Thomas J; Sprenger, Cynthia C; Plymate, Stephen R et al. (2014) Prostate cancer xenografts engineered from 3D precision-porous poly(2-hydroxyethyl methacrylate) hydrogels as models for tumorigenesis and dormancy escape. Biomaterials 35:8164-74
Chéry, Lisly; Lam, Hung-Ming; Coleman, Ilsa et al. (2014) Characterization of single disseminated prostate cancer cells reveals tumor cell heterogeneity and identifies dormancy associated pathways. Oncotarget 5:9939-51
Lucas, Jared M; Heinlein, Cynthia; Kim, Tom et al. (2014) The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis. Cancer Discov 4:1310-25
Gordon, Ryan R; Wu, Mengchu; Huang, Chung-Ying et al. (2014) Chemotherapy-induced monoamine oxidase expression in prostate carcinoma functions as a cytoprotective resistance enzyme and associates with clinical outcomes. PLoS One 9:e104271
Tang, Xi; Mahajan, Sumit S; Nguyen, Liem T et al. (2014) Targeted inhibition of cell-surface serine protease Hepsin blocks prostate cancer bone metastasis. Oncotarget 5:1352-62
Vela, I; Morrissey, C; Zhang, X et al. (2014) PITX2 and non-canonical Wnt pathway interaction in metastatic prostate cancer. Clin Exp Metastasis 31:199-211
Chevillet, John R; Kang, Qing; Ruf, Ingrid K et al. (2014) Quantitative and stoichiometric analysis of the microRNA content of exosomes. Proc Natl Acad Sci U S A 111:14888-93
Thadani-Mulero, Maria; Portella, Luigi; Sun, Shihua et al. (2014) Androgen receptor splice variants determine taxane sensitivity in prostate cancer. Cancer Res 74:2270-82
Yu, X; Cates, J M; Morrissey, C et al. (2014) SOX2 expression in the developing, adult, as well as, diseased prostate. Prostate Cancer Prostatic Dis 17:301-9

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