肺腺癌较肺鳞癌更容易发生脊柱转移，但其机制一直未能阐明。申请者前期研究发现与肺鳞癌比较，肺腺癌脊柱转移癌旁松质骨中高表达趋化因子CXCL17，而肺腺癌脊柱转移癌组织中存在M2型巨噬细胞浸润。此外，与肺鳞癌细胞比较，肺腺癌细胞高表达和分泌CXCL17，其可活化Src/FAK通路招募单核巨噬细胞，而M2型巨噬细胞可促进肺腺癌细胞增殖。抑制M2型巨噬细胞浸润可以明显降低肺腺癌脊柱转移灶的数量。因此，申请者推测肺腺癌细胞可以通过分泌CXCL17招募肿瘤微环境中的单核巨噬细胞，从而促进肺腺癌细胞在脊柱转移灶中增殖。本项目拟进一步在细胞水平分析CXCL17招募单核巨噬细胞的作用和分子机制；采用肺原位移植瘤的肺腺癌脊柱转移裸鼠模型，动态观察肺腺癌脊柱转移灶形成过程，验证CXCL17促脊柱转移的作用和机制；最后通过临床标本证实CXCL17在肺腺癌脊柱转移中的临床意义，为干预肺腺癌脊柱转移提供新的实验依据。

Lung adenocarcinoma is more likely to have spinal metastases than lung squamous cancer, but its mechanism has not been elucidated. Applicant's preliminary study found that CXCL17， one sort of chemokines, was highly expressed in cancellous bone adjacent to spinal metastases of lung adenocarcinoma, and there was M2 macrophages infiltration in cancer tissue. Compared with lung squamous carcinoma, lung adenocarcinoma cells expressed more CXCL17, which could recruit mononuclear macrophages by activating Src/FAK pathway. On the other hand, M2 macrophages could promote the proliferation of lung adenocarcinoma cell. Inhibition of M2 macrophages infiltration could significantly reduce the number of spinal metastases sites in lung adenocarcinoma. In view of this, we hypothesize that lung adenocarcinoma cells in spinal metastases may attract mononuclear macrophages in the tumor microenvironment by secreting CXCL17, thereby promoting the proliferation of lung adenocarcinoma cells in spinal metastases. Based on the previous study, we are planning to study the role and the molecular mechanisms of CXCL17 in the recruitment of mononuclear macrophages at the cellular level; to dynamically observe the formation of spinal metastases in lung adenocarcinoma using nude mouse model and to verify the role and mechanism of promoting spinal metastases by CXCL17; to verify the clinical significance of CXCL17 in spine metastases of lung adenocarcinoma using clinical specimens, which could provide a new experimental basis for intervention in spine metastases of lung adenocarcinoma.