Exosomal CXCL14 Contributes to M2 Macrophage Polarization through NF-κB Signaling in Prostate Cancer

Chemokine (C-X-C motif) ligand 14 (CXCL14) plays a critical role in maintaining homeostasis and inflammation in the local cell environment and regulating cancer progression. However, the role of CXCL14 in prostate cancer (PC) has not been fully investigated. In this study, the expression of CXCL14 was determined in PC tumor tissues by qRT-PCR and immunohistochemistry assay. Wound healing, invasion, colony formation, cell proliferation, and apoptosis assays were performed to evaluate the role of CXCL14 in PC progression. Exosomes were isolated from PC cell-condition medium by using ultracentrifugation assay and identified by using transmission electron microscopy and nanoparticle tracking analysis. M2 macrophage polarization-associated genes were measured by using qRT-PCR and Western blot assays. A PC xenograft mouse model was used to assess the role of CXCL14 in tumor growth in vivo. The results showed that CXCL14 was significantly upregulated in PC tissues and was positively correlated with pathological stages, lymph node metastasis, and angiolymphatic invasion. The positive correlations were also observed between CXCL14 and PD-L1 and IL-10. Knockdown CXCL14 dramatically inhibited PC cell proliferation, invasion, and colony formation, but not apoptosis. CXCL14 promoted M2 macrophage polarization through the NF-κB signaling pathway and exosome-mediated mechanism. Moreover, CXCL14 knockdown inhibited tumor growth in vivo. Taken together, exosomal CXCL14 promoted M2 macrophage polarization through the NF-κB signaling pathway and contributed to PC progression.