Cancer Metastases Formation in Bone
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    Cancer Metastases Formation in Bone
    Project Description

    The central aim of this research proposal is to build a multiscale in silico computational .modeling platform. for investigation of the metastasis of cancer to bone, with special emphasis on the regulatory role of the transforming growth factor beta (TGF-be). This modeling platform will consist of a variety of mathematical models that accurately reproduce and predict complex biological interactions between tumor cells, cells of the bone microenvironment, and multiple regulatory factors involved in bone destruction and tumor growth. The model will be flexible and multiscale, and will include ligand receptor interactions, as well as cell proliferation, differentiation, migration, apoptosis, communications, and evolution of tumor phenotypes over time. The project will bring together the expertise of two modeling groups (one located at Vanderbilt University and one at The University of Melbourne), each with complementary capabilities (one in cell-based modeling of cancer tumor morphogenesis in the Vanderbilt group and cell-cell signaling in bone remodeling processes in both normal and abnormal states in the Melbourne group) in close collaboration with experimentalists in the Vanderbilt Center for Bone Biology. The experimental program will provide state-of-the-art insights into cellular mechanisms that can be incorporated into the multi-scale model, and will validate the models by experiments designed in close collaboration with the modeling group. The ultimate goal is an integrated model of bone and cancer biology that can mimic in vivo processes faithfully enough for the model to serve as a hypotheses generation and screening tool, and in the distant future, as a tool for evaluating clinical procedures and their expected outcomes. The models will be shared with other research groups by distributing them in the Physiome CELL markup language.

    The proposed research id designed to integrate knowledge about bone reforming processes and their interaction with cancers into a comprehensive, predictive tool. Eventually, we expect that this model will have clinical uses, such as being able to predict the course of bone disease, offer mechanistic understanding of observed behavior, suggest new therapeutic approaches, and evaluate the effectiveness of current treatment strategies.


        Groovy biomedical image Proposed vicious cycles between cancer and host cells in the microenvironment at the bone metastatic site, in which soluble factors serve as key mediators communicating among cancer cells, host endothelial cells, inflammatory cells, and bone cells  

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Last updated: July 15 2015 09:16:54.