乳腺癌骨转移是制约晚期乳腺癌患者治疗的主要瓶颈，但乳腺癌细胞如何在骨内定植形成转移灶的机制尚未阐明。研究发现Annexin A2能够被多种炎症诱导表达，且其在造血干细胞粘附骨髓憩室的过程中起到关键作用，而肿瘤细胞骨内归巢的过程与造血干细胞相似。我们前期研究发现，与骨转移能力弱的MCF7细胞相比，骨转移能力强的MDA-MB-231细胞的Annexin A2及其受体表达均明显升高，乳腺癌骨转移裸鼠较对照鼠股骨内Annexin A2表达明显升高。本项目拟通过肿瘤细胞-巨噬细胞共培养体系、基因敲除, 粘附实验以及裸鼠体内乳腺癌骨转移瘤模型阐明炎症因子与Annexin A2相互作用进而增强肿瘤细胞骨内粘附，促进乳腺癌骨转移的具体分子机制，为治疗乳腺癌骨转移提供新的靶点。

Breast cancer with bone metastasis is the main obstacle to advanced breast cancer therapy. However, the molecular mechanism underlying breast cancer cells adhesion to bone forming metastasis has not been elucidated. Recent study has demonstrated that Annexin A2 could be induced by a variety of inflammation. Furthermore, Annexin A2 regulates the initial adhesion of hematopoietic stem cells to bone marrow, which was similar to tumor cells adhesion and homing to bone. Our previous work found that protein expression levels of Annexin A2 and its receptor were both up-regulated in strongly bone-metastatic MDA-MB-231 breast cancer cells than in weakly metastatic MCF7 cells. Moreover, Annexin A2 expression level in nude mice femurs with breast cancer metastasis was obviously higher than that in femurs without breast cancer metastasis. Here, we will carry out tumor cells-macrophages co-culture system, gene knockout, adhesion assays as well as animal experiments to reveal that interaction of inflammatory factors and Annexin A2 promotes breast cancer cells bone adhesion followed by bone metastasis, which will provide new targets for the treatment of breast cancer bone metastasis.