Role of Osteonectin in Breast Cancer Bone Metastasis

描述（由申请人提供）：本研究的长期目标 建议是阐明乳腺癌转移到骨的机制。 大约60%-70%的乳腺癌患者已经死亡或 死于乳腺癌的人骨转移骨粘连蛋白（OSN，BMT，BM-40） 一种骨因子，已被发现是乳房的化学引诱剂， 前列腺癌细胞此外，在小鼠中发现OSN表达增加， 然而，乳腺癌中OSN表达的增加与乳腺癌的发生有关， 癌细胞和骨转移尚未得到证实。令人惊讶的是，一个细胞 表面受体还有待鉴定。这一提议将考验中央 乳腺癌细胞中OSN表达增加的假设 肿瘤生长和骨转移，以及OSN与其细胞表面的结合 受体对这一过程至关重要。具体目标1将确定是否 乳腺癌细胞中OSN表达的改变将影响肿瘤细胞生长， 体外侵袭和蛋白酶活性以及特异性目的2将检查这是否 OSN表达的改变影响乳腺脂肪垫中肿瘤细胞的生长， 骨和体内骨转移。具体目标3将确定， 结合到细胞表面并表征细胞表面结合蛋白。一 将利用各种方法来阐明OSN在乳腺癌中的作用， 癌症骨转移和鉴定OSN表面结合蛋白。 OSN结合蛋白的鉴定和确定OSN结合蛋白的作用 乳腺癌细胞内源性产生OSN可能导致更好的 用于乳腺癌的诊断和/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.