BREAST CANCER AND BONE METASTASIS

描述：（改编自研究者摘要）一些实体瘤 例如特别倾向于引起溶骨性乳腺癌 转移 研究人员已经开发了一种体内模型来研究 人乳腺癌细胞形成溶骨性骨的能力 使用其他人开发的技术的改进的体内病变 研究动物肿瘤骨转移的机制。 人乳腺 将癌细胞接种到裸鼠心脏的左心室中， 小鼠，然后在以下期间评估溶骨性骨病变 4周后，通过X线和定量检查发现椎骨和四肢 组织学 申请人计划使用该模型来表征 人类乳腺癌细胞的特性， 转移和溶骨性骨破坏。 特别是，他们计划 研究培养的人类乳腺癌细胞的特性， 可能与骨转移和骨质溶解有关，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产生。 他们还计划 使用这个模型来检查潜在的治疗方法， 或抑制溶骨性骨损伤的发展。 通过这个模型，他们将选择具有增强的细胞亚群， 引起溶骨性骨破坏的能力，研究 细胞附着蛋白如层粘连蛋白和E-钙粘蛋白， 特异性拮抗剂、抗体和转染细胞，以及 基质金属蛋白酶及其抑制剂在骨溶解中的作用 人类乳腺癌细胞在这个模型中。 总体目标是 找出一些分子机制， 骨溶解，以便合理的治疗方法， 旨在预防或逆转与骨破坏相关的 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.