Periostin是一主要由基质细胞分泌的细胞外基质蛋白，在组织损伤修复、炎症反应、组织纤维化以及肿瘤发生发展中均起重要作用。已有研究表明，Periostin可通过参与乳腺癌肿瘤干细胞微环境、肺转移前微环境和肺血管周微环境的形成来促进乳腺癌细胞肺转移。我们的初步结果表明，Periostin在乳腺癌细胞骨转移骨髓组织中高表达，敲除Periostin可抑制破骨细胞分化成熟，抑制乳腺癌细胞骨转移，但对Periostin是如何促进乳腺癌细胞骨转移并不清楚。本项目将应用乳腺癌细胞骨转移小鼠模型、Periostin基因敲除小鼠和Periostin重组蛋白处理等模型，研究Periostin蛋白对破骨细胞分化成熟、成骨细胞功能以及乳腺癌细胞粘附、生存和增殖的影响及分子机制，从骨组织微环境重塑角度阐明Periostin蛋白促进乳腺癌细胞骨转移的分子机制，为乳腺癌骨转移的预防和治疗提供实验依据和新的作用靶点。

Extracellular matrix protein periostin is mainly secreted by stromal cells and plays an important role in tissue repair, inflammation, fibrosis and tumor progression. Previous studies have shown that periostin can promote lung metastasis of breast cancer cells by participating in the formation of breast cancer stem cell niche, pre-metastasis niche and perivascular niche. Our preliminary results show that periostin is highly expressed in the bone marrow of mice with bone metastasis of breast cancer. Knocking out periostin can inhibit the differentiation and maturation of pre-osteoclasts and bone metastasis of breast cancer cells; however, it is still not clear how periostin promotes bone metastasis of breast cancer cells. This project will use distinct mouse models of bone metastasis of breast cancer cells, periostin-knockout mice and periostin recombinant protein treatment to investigate the effects and molecular mechanisms of periostin on the differentiation and maturation of pre-osteoclasts, the function of osteoblasts and the adhesion, survival and proliferation of breast cancer cells during bone metastasis of breast cancer. We will also elucidate the molecular mechanism of periostin in promoting bone metastasis of breast cancer cells from the perspective of bone tissue microenvironment remodeling. This study will provide experimental evidence and a novel molecular target for the prevention and treatment of bone metastasis of breast cancer.