The Effect and Mechanism of Spine Metastases Induced by CXCL17 from Lung Adenocarcinoma Cells

Background: Spine metastases are common in patients with lung adenocarcinoma (LUAD). Improving outcome of spine metastatic LUAD patients require uncovering mechanism of metastases. In this context, we tried to decipher the effect and mechanism of CXCL17 in spine metastases caused by LUAD. Methods: Clinical tumor tissues, lung cancer cell lines and TCGA dataset were utilized to analyze the expression of CXCL17. Transwell assay was used to confirm chemotaxis of mononuclear macrophages induced by CXCL17. Western blotting was performed to study the mechanism of mononuclear macrophages chemotaxis towards CXCL17. Cell counting Kit- 8 assay was employed to investigate the effect of conditioned medium from M1 and M2 macrophages on the proliferation of lung cancer cell lines. Findings: We proved that higher CXCL17 was expressed in clinical tumor tissues and lung cancer cell lines from LUAD than those from lung squamous cell carcinoma. Moreover, we found that CXCL17 increased migration ability of THP-1 cells through activating Src/FAK pathway. In addition, conditioned medium from M2 macrophages promoted proliferation of lung cancer cell lines. Interpretation: CXCL17 is a key regulator of spine metastases caused by LUAD. CXCL17 and downstream Src/FAK pathway offer promising intervention targets for clinicians and researchers in this field. Funding: This work was supported by General Scientific Research Project of Zhejiang Education Department (Y201838964), and Project of medicine and health technology program in Zhejiang province (2019314900). Declaration of Interest: The authors declare no potential conflicts of interest. Ethical Approval: All procedures were deployed with the signed consent form the patients and approval of the Ethics Committee of the Second Affiliated Hospital of Zhejiang University.