Prostate Cancer Bone Metastasis: Biology and Targeting

描述(由申请者提供)：这个来自埃默里大学医学院的多机构项目专注于阐明骨或前列腺基质细胞与恶性前列腺癌细胞之间相互作用所涉及的生物学和分子途径。该计划项目的主要主题是前列腺癌细胞与其微环境的相互作用以特定器官的方式决定肿瘤的生长、侵袭和转移。这表现在临床前列腺癌的骨转移中，肿瘤上皮和周围骨母细胞的增殖都被加速。通过了解这种相互作用的分子基础，可以开发新的治疗靶向策略来治疗前列腺癌的骨转移。该计划项目由3个项目和3个核心组成，旨在实现已有先前研究合作记录的科学家个人之间的协同作用。具体研究领域包括：项目1-Chung：分析细胞外基质(ECM)和整合素在前列腺癌生长和转移中的相互作用；项目2-Farach-Carson：评估硫酸乙酰肝素蛋白多糖(HSPG)、肝素结合生长因子(HB)及其受体在前列腺癌骨转移中的作用；项目3-Petros：测定线粒体DNA(MtDNA)突变对前列腺癌生长和转移的影响，特别侧重于mtDNA突变在前列腺癌细胞中的抗凋亡功能。每个项目都有自己的目标主题，并将相互协作，实现开发基于机制的合理治疗方法治疗前列腺癌骨转移的目标。该方案项目得到三个核心的支持：行政和生物统计学核心A-Chung、动物和组织培养核心B-Martin和病理学和实验室支持核心C-AMIN。该计划项目的最终目标是基于对前列腺癌以及前列腺癌和骨基质相互作用的机械性理解，开发新的诊断、预后和治疗模式。

DESCRIPTION (provided by applicant): 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.