Mechanism of lung adenocarcinoma spine metastasis induced by CXCL17.

PURPOSE:Spine metastases are common in patients with lung adenocarcinoma (LUAD). Improving the clinical outcome of spine metastasis LUAD patients requires knowledge on the mechanism underlying the metastatic process. Here, we sought to decipher the effect and mechanism of C-X-C motif chemokine ligand 17 (CXCL17) on LUAD spine metastasis. METHODS:Clinical tumor tissue samples, lung cancer cell lines and a TCGA dataset were used for CXCL17 expression analyses. A transwell invasion assay was used to assess the chemotaxis capacity of mononuclear macrophages induced by CXCL17. Western blotting was performed to explore the mechanism of mononuclear macrophage chemotaxis towards CXCL17. A 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 cells. RESULTS:We found that the expression of CXCL17 was higher in clinical LUAD samples and LUAD cell lines than in lung squamous cell carcinoma (LUSC) samples and cell lines. Moreover, we found that CXCL17 increased the migration of THP-1 mononuclear macrophages by activating the Src/FAK pathway. In addition, we found that conditioned medium from M2 macrophages promoted the proliferation of LUAD cells. CONCLUSIONS:From our data we conclude that CXCL17 is a key regulator of LUAD spine metastasis. CXCL17 and its downstream Src/FAK pathway may serve as clinical intervention targets.

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