The Expression Of CC-chemokine Ligand 18 In Prostate Cancer And Its Clinical Significance

Purpose: CC-chemokine ligand 18(CCL18), produced by tumor-associated macrophages, promotes malignant behaviors of various human cancer types. However, its involvement in human prostate cancer(PCa) has not been fully elucidated. The aim of this study was to investigate the expression patterns, the clinical significance and the oncogenic roles of CCL18 in PCa. Methods: Expression of CCL18 at mRNA and protein levels was respectively detected by using real-time quantitative reverse transcriptase-polymerase chain reaction(qRT-PCR) and immunohositochemistry analysis for preliminary detection. Then further analyze the associations of CCL18 expression with clinicopathological features and clinical outcome of 80 human prostate cancer tissues and 95 non-cancerous prostate tissues. The role of CCL18 in PCa cell migration and invasion was analyzed by cell-migration assay and matrigel invasion assay. The effects of CCL18 on apoptosis of PCa cells were also tested. The efficiency of CCL18 on prostate tumor growth was further assessed in a subcutaneous xenograft model. Results: Both qRT-PCR and immunohistochemistry analysis found that CCL18 expression were upregulated(both P<0.01) in PCa tissues compared with those in non-cancerous prostate tissues. In addition, the upregulation of CCL18 was significantly correlated with high Gleason score(P=0.034) of patients with PCa. Moreover, rCCL18 stimulation in LNCaP and DU145 cells promoted cell migration and invasion. Flow cytometry showed that CCL18 overexpression in DU145 cells induced cell apoptosis rate decreased. Furthermore, subcutaneous homografts in mice models showed the increased tumor growth in the CCL18 stimulation mice. And the expression of Ki67(P<0.01), PCNA(P<0.01) in CCL18 stimulation mice are significantly increased.Conclusions: Our data offer the evidence for the first time that the upregulation of CCL18 may be involved in the malignant progression of PCa.