肺癌是全球发病率和死亡率最高的恶性肿瘤，骨是肺癌最常见的转移部位。肺癌骨转移引起骨痛、骨折、神经压迫，患者极度痛苦，死亡率高。但肺癌骨转移的生物学机制目前尚不清楚。CCL7在肿瘤发生、转移、微环境形成中发挥着重要作用，项目组利用单细胞测序技术发现一个高表达CCL7的干细胞亚群；利用流式分选各细胞群体并进行左心室注射，我们进一步发现高表达CCL7的干细胞亚群具有显著的骨转移倾向；并且该亚群的条件培养基能促进破骨前体细胞向成熟破骨细胞分化，而干扰CCL7表达后的条件性培养基则失去了破骨分化诱导能力；我们还发现CCL7可以结合NF-κB，过表达CCL7能显著增加NF-κB细胞核转位。课题组计划从大量（≥100例）肺癌骨转移临床样本入手，从分子、细胞、动物水平阐明CCL7通过调控NF-κB的转录活性，以此揭示CCL7介导肺癌骨转移恶性生物学行为的分子机制，为肺癌骨转移的治疗提供理论依据和药物靶点。

Lung cancer is one of the most common malignant tumors and the leading cause of cancer-related death. Distant metastasis is the main cause of death for non-small cell lung cancer (NSCLC) patients, with the bone as a more frequent metastatic site. Patients with bone metastasis often experience severe pain, pathologic bone fracture, spinal cord compression, and hypercalcemia, which entail poor quality of life, decrease the survival rate, and increase health care costs substantially. However, the pathological mechanism underlying bone metastasis in lung cancer remains poorly understood. CCL7 plays a pivotal role in tumorigenesis. CCL7 promotes tumor progression by supporting the formation of the tumor microenvironment and facilitating tumor invasion and metastasis. Our team found a NSCLC cell subset with high CCL7 expression by using single-cell sequencing data. The conditioned medium from the subset with the ability to enhances osteoclast precursor fusion and osteoclast formation. This ability can be blocked by CCL7 inhibitor. We also found that CCL7 could bind IκBα, a inhibitory factor of NF-κB. CCL7 overexpression leads to increase of nuclear transfer of NF-κB. The aim of the present study was to detect the malignant biological role and the downstream of CCL7 in lung cancer in order to provides insights into lung cancer bone metastasis and look for potential therapeutic target.