BREAST CANCER AND BONE METASTASIS

描述：(改编自《调查者摘要》)一些实体肿瘤 例如乳腺癌有引起骨溶解特殊倾向 转移瘤。研究人员开发了一种活体模型来研究 人乳腺癌细胞形成溶骨骨的能力 使用他人开发的技术改进的活体损伤 目的研究动物肿瘤骨转移的机制。人类乳房 癌细胞接种到裸鼠心脏的左心室内 小鼠，然后在以下过程中评估溶骨性骨损伤 在椎骨和四肢进行4周的x光和定量 组织学。申请者计划使用此模型来描述 与骨骼有关的人乳腺癌细胞的特性 转移和溶骨性骨破坏。特别是，他们计划 目的：研究培养的人乳腺癌细胞的特性 可能与骨转移和骨溶解有关，包括表达 与层粘连蛋白、E-钙粘蛋白和 蛋白水解酶或其抑制剂的生产。他们还计划 使用这个模型来检查潜在的治疗方法来预防 或抑制溶骨性骨损的发展。 有了这个模型，他们将选择具有增强的细胞亚群 导致溶骨性骨破坏的能力，调查其作用 层粘连蛋白和E-钙粘附素等细胞附着蛋白的作用 特异性拮抗剂、抗体和转基因细胞及其作用 基质金属蛋白酶及其抑制物在骨质疏松症中的作用 人乳腺癌细胞在这个模型中。总体目标是 确定这些分子机制中的一些负责 体内溶骨，使合理的治疗方法得以 旨在防止或逆转与以下疾病相关的骨破坏 转移性乳腺癌。

DESCRIPTION: (Adapted From Investigator's Abstract) Some solid tumors such as breast cancer have a special predilection to cause osteolytic metastases. The investigators have developed an in vivo model to study the capacity of human breast cancer cells to form osteolytic bone lesions in vivo using a modification of a technique developed by others to study mechanisms of bone metastasis by animal tumors. Human breast cancer cells are inoculated into the left ventricle of the heart of nude mice, and osteolytic bone lesions are then assessed during the following 4 weeks in the vertebrae and extremities by x-ray and quantitative histology. The applicants plan to use this model to characterize the properties of human breast cancer cells which are responsible for bone metastasis and osteolytic bone destruction. In particular, they plan to study specific properties of cultured human breast cancer cells which may be related to metastasis to bone and osteolysis, including expression of cell attachment proteins which bind to laminin, to E-cadherin and the production of proteolytic enzymes or their inhibitors. They also plan to use this model to examine potential therapeutic approaches to prevent or inhibit the development of osteolytic bone lesions. With this model, they will select subpopulations of cells with enhanced capacity to cause osteolytic bone destruction, investigate the role of cell attachment proteins such as laminin and E-cadherin by the use of specific antagonists, antibodies and transfected cells, and the role of matrix metalloproteases and their inhibitors in osteolysis caused by human breast cancer cells in this model. The overall goal is to identify some of these molecular mechanisms which are responsible for osteolysis in vivo, so that rational therapeutic approaches can be devised to prevent or reverse bone destruction associated with metastatic breast cancer.