Prostate Cancer Bone Metastasis: Biology and Targeting

描述（由申请人提供）：这个来自埃默里大学医学院的多机构计划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的生物学和分子途径。 该计划项目的首要主题是前列腺癌细胞与其微环境的相互作用以器官特异性方式决定肿瘤生长，侵袭和转移。 这表现在临床前列腺癌骨转移中，其中肿瘤上皮细胞和周围骨成骨细胞的增殖加速。 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骨转移。 该计划项目包括3个项目和3个核心，旨在实现已经建立了先前研究合作记录的科学家之间的协同作用。 具体研究领域包括：项目1-Chung：前列腺癌生长和转移中细胞外基质（ECM）和整合素相互作用的分析;项目2-Farach-Carson：硫酸乙酰肝素蛋白聚糖（HSPG）、肝素结合（HB）生长因子及其受体在前列腺癌骨转移中的作用评估;项目3-彼得罗斯：线粒体DNA（mtDNA）突变对前列腺癌生长和转移的影响的测定，特别关注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靶向主题，并将相互协作，以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。 该计划项目由三个核心支持：行政和生物统计核心A-Chung，动物和组织培养核心B-Martin以及病理学和实验室支持核心C-Amin。 该项目的最终目标是在对前列腺肿瘤和前列腺与骨基质相互作用的机理理解的基础上，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.