BREAST CANCER AND BONE METASTASIS

乳腺癌和骨转移

• 批准号: 2008515
• 负责人: TOSHIYUKI YONEDA
• 金额: $ 15.6万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-03-10 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2008515
• 关键词: athymic mouse; bone neoplasms; breast neoplasms; cadherins; disease /disorder model; histology; laminin; metastasis; protease inhibitor; tissue /cell culture; transfection

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.

描述：（改编自研究者摘要）一些实体瘤 例如乳腺癌特别容易引起溶骨 转移。 研究人员开发了一种体内模型来研究 人类乳腺癌细胞形成溶骨性骨的能力 使用他人开发的技术的改进进行体内损伤 研究动物肿瘤骨转移的机制。 人体乳房 癌细胞被接种到裸心左心室 然后在以下过程中评估小鼠和溶骨性骨损伤 4 周，通过 X 射线和定量检测椎骨和四肢 组织学。 申请人计划使用该模型来表征 负责骨骼的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定特性 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 使用该模型来检查潜在的治疗方法以预防 或抑制溶骨性骨病变的发展。 通过这个模型，他们将选择具有增强的细胞亚群 导致溶骨性骨质破坏的能力，调查其作用 细胞附着蛋白，例如层粘连蛋白和 E-钙粘蛋白，通过使用 特异性拮抗剂、抗体和转染细胞，以及其作用 基质金属蛋白酶及其抑制剂在骨溶解中的作用 该模型中的人类乳腺癌细胞。 总体目标是 确定其中一些分子机制 体内骨质溶解，以便可以采取合理的治疗方法 旨在预防或逆转与以下疾病相关的骨质破坏 转移性乳腺癌。