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University of Michigan

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Overview

     Welcome to the University of Michigan Biology of Skeletal Metastasis Program Project website. This program was established in April 2004 through funding by the National Cancer Institute and is currently one of only three cancer:bone interaction Program Projects in the United States. This comprehensive research program involves cross-disciplinary interactions among basic scientists through clinical researchers experienced in cancer and bone biology.

     The common occurrence and serious outcome of prostate cancer skeletal lesions has prompted the National Cancer Institute Prostate Cancer Progress Review Group to state that there is a need to study prostate cancer skeletal metastasis and a need of animal models to address this disease. We are attacking this problem by combining experts in prostate cancer research with bone metabolism experts in a Program, led by Dr. Evan Keller, that combined four interrelated projects supported by three program cores. Our ultimate goal is to define the cellular and molecular mechanisms that lead to prostate cancer skeletal metastases. The central theme of our Program is that there is crosstalk between the bone microenvironment and prostate cancer cells that fosters the development of prostate cancer bone metastasis. These properties include a combination of factors that cause prostate cancer cells to invade into bone and enhance their ability to thrive in the bone microenvironment. To accomplish these goals, we are pursuing the following interactive projects: Project 1 entitled "Role of SDF-1/CXCR4 in bone metastasis", directed by Dr. Russel Taichman, explores the role of chemotactic mechanisms through which prostate cancer cells home and adhere to bone marrow, with a specific focus on the chemokine, stromal derived factor-1 (SDF), and its receptor, CXCR4. Project 2, entitled “The role of PAR1 in prostate cancer cell motility and invasion”, directed by Dr. Kenneth Pienta, explores the postulation that protease-activated receptor-1 (PAR-1) promotes motility of cancer cells and extravasation into the bone site. Project 3, entitled “BMPs and prostate cancer skeletal metastases”, directed by Dr. Evan Keller, tests the hypothesis that bone morphogenetic protein is a critical mediator for the establishment of prostate cancer skeletal metastases. Project 4, entitled “PTHrP as a mediator of the osseous response to metastatic prostate cancer”, directed by Dr. Laurie McCauley, examines the role of PTHrP and its ability to alter the microenvironment at prostate cancer bone metastatic sites through increasing bone remodeling. Core A (Administration), directed by Dr. Keller, coordinates reporting, evaluation, and committee activities, facilitate interactions among the projects and provide biostatistical support with Mr. Rodney Dunn and Ms. Stephanie Faruzzi. Core B (Animals), directed by Dr. Keller provides all the projects with the mouse animal models, assistance with animal research techniques, management of animal housing and veterinary evaluation of all animals used in the program, and scientific input into animal model design and interpretation of results. Core C (Bone), directed by Dr. McCauley, provides expertise with bone techniques including bone histomorphometry and histology, radiography and bone densitometry. The Program also has direct interaction with the University of Michigan SPORE in Prostate Cancer Pathology Core, directed by Dr. Rajal Shah.


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