Role of Osteonectin in Breast Cancer Bone Metastasis

骨连接素在乳腺癌骨转移中的作用

• 批准号: 6685697
• 负责人: JENNIFER E KOBLINSKI
• 金额: $ 4.53万
• 依托单位: U.S. NAT'L INST/DENTAL/CRANIOFACIAL RES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-11-16 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6685697
• 关键词: affinity chromatography; antisense nucleic acid; athymic mouse; binding proteins; bone neoplasms; breast neoplasms; cell line; cell surface receptors; endopeptidases; enzyme activity; immunocytochemistry; immunoprecipitation; metastasis; neoplasm /cancer invasiveness; neoplastic growth; osteonectin; surface plasmon resonance; transfection

DESCRIPTION (provided by applicant): The long-term goal of this research proposal is to elucidate mechanisms of breast cancer metastasis to bone. Approximately, 60-70 percent of breast cancer patients who have died or are dying of breast cancer have bone metastases. Osteonectin (OSN, SPARC, BM-40) is a bone factor that has been found to be a chemo-attractant for breast and prostrate cancer cells. In addition, increased OSN expression has been found in breast cancer, however a connection between increased OSN expression in breast cancer cells and bone metastasis has not been proven. Surprisingly, a cell surface receptor has yet to be identified. This proposal will test the central hypothesis that increased expression of OSN in breast cancer cells increases tumor growth and metastasis to bone, and binding of OSN to its cell surface receptor is important for this process. Specific aim 1 will determine if altered expression of OSN in breast cancer cells will affect tumor cell growth, invasion and protease activity in vitro and specific aim 2 will examine if this altered expression of OSN affects tumor cell growth in the mammary fat pad, in bone and in metastasis to bone in vivo. Specific aim 3 will establish if OSN binds to the cell surface and characterize the cell surface binding protein. A variety of approaches will be utilized to elucidate the role OSN in breast cancer bone metastasis and to identify OSN surface binding proteins. Identification of the OSN binding protein and determining the role of endogenous production of OSN by breast cancer cells may lead to better diagnostic and/or therapeutic approaches for breast cancer.

描述（由申请人提供）：这项研究的长期目标 建议是阐明乳腺癌转移对骨骼的机制。 大约有60-70％的乳腺癌患者死亡或 乳腺癌的死亡患有骨转移。 Osteonectin（OSN，SPARC，BM-40）是 骨因子已被发现是乳房的化学吸引者 俯卧癌细胞。此外，在 但是，乳腺癌，但是乳房中OSN表达增加之间的联系 癌细胞和骨转移尚未得到证明。令人惊讶的是，一个单元格 表面受体尚未确定。该建议将测试中央 假设乳腺癌细胞中OSN表达增加的假设增加 肿瘤生长和向骨的转移，以及OSN与其细胞表面结合 受体对于此过程很重要。具体目标1将确定是否 OSN在乳腺癌细胞中的表达改变会影响肿瘤细胞的生长， 体外和特定目标2的入侵和蛋白酶活性将检查是否 OSN表达的改变会影响乳腺脂肪垫中的肿瘤细胞生长， 骨和转移到体内骨骼的转移中。特定目标3将确定OSN是否 结合细胞表面并表征细胞表面结合蛋白。一个 各种方法将用于阐明乳房中的角色OSN 癌骨转移并鉴定OSN表面结合蛋白。 鉴定OSN结合蛋白并确定 乳腺癌细胞对OSN的内源性产生可能会导致更好 乳腺癌的诊断和/或治疗方法。