This multi-institutional Program Project from the Emory University School of Medicine focuses on the elucidation of the biology and molecular pathways involved in the interaction between stromal cells of the bone or the prostate and malignant prostate cancer cells. The overarching theme of this Program Project is that prostate cancer cell interaction with its microenvironment determine tumor growth, invasion, and metastasis in an organ-specific manner. This is manifested in clinical prostate cancer bone metastasis where the proliferation of both tumor epithelium and surrounding bone osteoblasts are accelerated. By understanding the molecular basis of this interaction, novel therapeutic targeting strategies can be developed to treat prostate cancer bone metastasis. This Program Project comprises of 3 Projects and 3 Cores and is organized to achieve synergy among the individual scientists who already have an established track record of prior research collaborations. Specific areas of investigation are: Project 1-Chung: the analysis of extracellular matrix (ECM) and integrin interaction in prostate cancer growth and metastasis; Project 2-Farach-Carson: the assessment of the roles of heparan sulfate proteoglycan (HSPG), heparin binding (HB) growth factors and their receptors in prostate cancer bone metastasis; Project 3-Petros: the determination of the effect of mitochondrial DNA (mtDNA) mutations on prostate cancer growth and metastasis, with specific focus on the anti-apoptotic function of mtDNA mutations in prostate cancer cells. Each of the projects has its own targeting theme and collaboratively will interact and achieve the goal of developing mechanism-based rational therapeutic approaches for the treatment of prostate cancer bone metastasis. This Program Project is supported by three Cores: the Administrative and Biostatistical Core A-Chung, the Animal and Tissue Culture Core B-Martin and the Pathology and Laboratory Support Core C-Amin. The ultimate goal of this Program Project is to develop novel diagnostic, prognostic and treatment modalities based on a mechanistic understanding of prostate tumor and prostate and bone stroma interaction.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA098912-02
Application #
6801786
Study Section
Subcommittee G - Education (NCI)
Program Officer
Mohla, Suresh
Project Start
2003-09-17
Project End
2008-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
2
Fiscal Year
2004
Total Cost
$1,469,563
Indirect Cost
Name
Emory University
Department
Urology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Rohena-Rivera, Krizia; Bhowmick, Neil A (2018) Notch inhibitor screening reveals an unexpected HES1 heterodimer. J Biol Chem 293:8295-8296
Tighiouart, Mourad; Cook-Wiens, Galen; Rogatko, André (2018) A Bayesian adaptive design for cancer phase I trials using a flexible range of doses. J Biopharm Stat 28:562-574
Madhav, Anisha; Andres, Allen; Duong, Frank et al. (2018) Antagonizing CD105 enhances radiation sensitivity in prostate cancer. Oncogene 37:4385-4397
Jan, Yu Jen; Chen, Jie-Fu; Zhu, Yazhen et al. (2018) NanoVelcro rare-cell assays for detection and characterization of circulating tumor cells. Adv Drug Deliv Rev 125:78-93
Grindel, Brian J; Martinez, Jerahme R; Tellman, Tristen V et al. (2018) Matrilysin/MMP-7 Cleavage of Perlecan/HSPG2 Complexed with Semaphorin 3A Supports FAK-Mediated Stromal Invasion by Prostate Cancer Cells. Sci Rep 8:7262
Jimenez, Jose L; Tighiouart, Mourad; Gasparini, Mauro (2018) Cancer phase I trial design using drug combinations when a fraction of dose limiting toxicities is attributable to one or more agents. Biom J :
Martinez, Jerahme R; Grindel, Brian J; Hubka, Kelsea M et al. (2018) Perlecan/HSPG2: Signaling role of domain IV in chondrocyte clustering with implications for Schwartz-Jampel Syndrome. J Cell Biochem :
Jolly, Mohit Kumar; Boareto, Marcelo; Debeb, Bisrat G et al. (2017) Inflammatory breast cancer: a model for investigating cluster-based dissemination. NPJ Breast Cancer 3:21
Masko, Elizabeth M; Alfaqih, Mahmoud A; Solomon, Keith R et al. (2017) Evidence for Feedback Regulation Following Cholesterol Lowering Therapy in a Prostate Cancer Xenograft Model. Prostate 77:446-457
Alfaqih, Mahmoud A; Allott, Emma H; Hamilton, Robert J et al. (2017) The current evidence on statin use and prostate cancer prevention: are we there yet? Nat Rev Urol 14:107-119

Showing the most recent 10 out of 215 publications