The Biology of Prostate Cancer Skeletal Metastases

描述（由申请人提供）：前列腺癌骨骼病变的常见发生率和严重结局促使美国国家癌症研究所前列腺癌进展审查小组指出，有必要研究前列腺癌骨骼转移，并需要动物模型来解决这种疾病。 不幸的是，在这一领域缺乏研究活动。 在目前的提案中，我们通过将前列腺癌研究专家与骨代谢专家结合在两个核心支持的四个相互关联的项目中来解决这个问题。 我们的最终目标是确定导致前列腺癌骨转移的细胞和分子机制。 我们计划的中心主题是骨微环境具有促进前列腺癌转移发展的独特特性。 这些特性包括导致前列腺癌细胞迁移并附着于骨并增强其在骨微环境中茁壮成长的能力的因素的组合。 为了发展这一主题，我们将执行以下互动项目：项目1将探索骨髓中基质衍生因子及其受体对前列腺癌细胞的作用，这些细胞有利于细胞转移到骨的能力。 项目2将发展蛋白酶激活受体1是前列腺癌骨转移的重要介质的主题。 项目3将研究骨形态发生蛋白促进成骨细胞病变发展的机制。 项目4将探讨甲状旁腺相关蛋白在转移部位成骨细胞病变发展中的作用。 这些项目将通过使用几种动物模型联系在一起，包括SCID-人和体内小骨发育。 动物模型及与动物有关的服务将由动物核心（核心A）以有效率及具成本效益的方式提供支援。 骨评价，包括组织形态测定、密度测定和放射成像将由骨芯（芯B）支持。

DESCRIPTION (provided by applicant): 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. Unfortunately, there is a dearth of research activity in this field. In the current proposal, we attack this problem by combining experts in prostate cancer research with bone metabolism experts in four interrelated projects supported by two 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 the bone microenvironment has unique properties that foster the development of prostate cancer metastasis. These properties include a combination of factors that cause prostate cancer cells to migrate and attach to bone and enhance their ability to thrive in the bone microenvironment. To develop this theme, we will perform the following interactive projects: Project 1 will explore the role of stromal-derived factor in the bone marrow and its receptor on the prostate cancer cells that favor the cells' ability to metastasize to bone. Project 2 will develop the theme that protease-activated receptor 1 is an important mediator of prostate cancer skeletal metastasis. Project 3 will examine the mechanisms through which bone morphogenetic proteins contribute to development of osteoblastic lesions. Project 4 will explore the role of parathyroid hormone-related protein on the development of osteoblastic lesions at the metastatic site. These projects will be tied together through use of several animal models including SCID-human and ossicle development in vivo. The animal model and animal-related services will be supported by the Animal Core (Core A) in an efficient and cost-effective manner. Bone evaluation, including histomorphometry, densitometry and radiographic imaging will be supported by a Bone Core (Core B).