Role of Osteonectin in Breast Cancer Bone Metastasis

描述(申请人提供)：本研究的长期目标 建议阐明乳腺癌骨转移的机制。 大约60%-70%的乳腺癌患者已经死亡或 死于乳腺癌有骨转移。骨连蛋白(OSN、SPARC、BM-40)是 一种已被发现对乳房和乳房有化学吸引力的骨骼因子 压倒癌细胞。此外，还发现OSN在 然而，乳腺癌与乳房中OSN表达增加之间的联系 癌细胞和骨转移之间的关系尚未得到证实。令人惊讶的是，一个细胞 表面受体尚未确定。这项提议将考验中央银行 乳腺癌细胞中OSN表达增加的假说 肿瘤的生长和向骨转移以及OSN与其细胞表面的结合 受体在这一过程中非常重要。具体目标1将决定是否 乳腺癌细胞中OSN表达的改变会影响肿瘤细胞的生长， 体外侵袭和蛋白水解酶活性和特异性目标2将检测这一点 OSN的表达变化影响乳腺脂肪垫中肿瘤细胞的生长 体内的骨转移和骨转移。特定目标3将确定OSN是否 结合到细胞表面，并表征细胞表面结合蛋白。一个 将使用多种方法来阐明OSN在乳房中的作用 肿瘤骨转移和鉴定OSN表面结合蛋白。 OSN结合蛋白的鉴定及其作用机制的研究 乳腺癌细胞内源性OSN的产生可能会导致更好的 乳腺癌的诊断和/或治疗方法。

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.