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

Abstract

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.

Development and experimental validation of an M2 macrophage and platelet‐associated gene signature to predict prognosis and immunotherapy sensitivity in bladder cancer

“…Interestingly, we found that the regulation of M2 macrophage polarization by platelets in the tumor microenvironment was not unique to BLCA; it was also observed in renal cancer cells but not in prostate cancer cells. Previous studies have reported that the renal cancer microenvironment promotes the polarization of M2 macrophages, 21 whereas prostate cancer polarizes macrophages in favor of M1 macrophages, 22 which is consistent with our experimental results; however, an opposing view has been published 23 . Our experimental results provide evidence to clarify this controversial issue from the perspective of platelet involvement.…”

“…however, an opposing view has been published. 23 Our experimental results provide evidence to clarify this controversial issue from the perspective of platelet involvement.…”

“…Previous studies have reported that the renal cancer microenvironment promotes the polarization of M2 macrophages, 21 whereas prostate cancer polarizes macrophages in favor of M1 macrophages, 22 which is consistent with our experimental results; however, an opposing view has been published. 23 Our experimental results provide evidence to clarify this controversial issue from the perspective of platelet involvement.…”

The role of proinflammatory cytokines and CXC chemokines (CXCL1–CXCL16) in the progression of prostate cancer: insights on their therapeutic management

“…5 ). Although it did not impact PCa cell death, its downregulation prevented PCa cells from proliferating and invading [ 226 ]. Additionally, CXCL14 knockdown suppressed tumor growth in vivo.…”

Exosomal NAT10 from esophageal squamous cell carcinoma cells modulates macrophage lipid metabolism and polarization through ac4C modification of FASN

“…Emerging evidence underscores that the transition of M1 to M2 macrophages can reprogram the macrophage landscape, activating malignant processes within cancer cells by shaping the tumor microenvironment. For instance, exosomal FGD5-AS1 has been shown to stimulate cell proliferation and migration in pancreatic cancer by promoting M2 polarization of TAMs [12] , while exosome-delivered CXCL14 induces M2 polarization of TAMs, fostering prostate cancer progression [13] . Previous studies have established that exosomes mediate the transfer of RNA or proteins to adjacent cells or tissues, orchestrating alterations in the tumor microenvironment and driving tumor progression [ 14 , 15 ].…”