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Lactate dehydrogenase isozyme (LDH) is a tetramer constituted of two isoforms, LDHA and LDHB, the expression of which is associated with cell metabolism and cancer progression. Our previous study reveals that CC-chemokine ligand-18 (CCL18) is involved in progression of prostate cancer (PCa).This study aims to investigate how CCL18 regulates LDH isoform expression, and therefore, contributes to PCa progression. The data revealed that the expression of LDHA was upregulated and LDHB was downregulated in PCa cells by CCL18 at both messenger RNA and protein levels. The depletion of CCR8 reduced the ability of CCL18 to promote the proliferation, migration, and lactate production of PCa cells. Depletion of a CCR8 regulated transcription factor, ARNT, significantly reduced the expression of LDHA. In addition, The Cancer Genome Atlas dataset analyses revealed a positive correlation between CCR8 and ARNT expression. Two dimension difference gel electrophoresis revealed that the LDHA/LDHB ratio was increased in the prostatic fluid of patients with PCa and PCa tissues. Furthermore, increased LDHA/LDHB ratio was associated with poor clinical outcomes of patients with PCa. Together, our results indicate that the CCR8 pathway programs LDH isoform expression in an ARNT dependent manner and that the ratio of LDHA/LDHB has the potential to serve as biomarkers for PCa diagnosis and prognosis., (© 2020 Wiley Periodicals, Inc.)

Background and Aim: CC chemokine ligand 18 (CCL18) promotes malignant behaviors of various human cancer types. However, its involvement in human prostate cancer has not been fully elucidated. The aim of this study was to investigate the role of CCL18 in PCa., Methods: Expression of CCL18 at mRNA and protein levels was detected using real-time qRT-PCR and immunohistochemistry analysis. We analyzed the associations of CCL18 expression with clinical features of human PCa. The effects of PCa cell migration, invasion, and apoptosis were tested. The efficiency of CCL18 on prostate tumor growth was assessed in a subcutaneous xenograft model., Results: CCL18 expression was upregulated (both P < 0.01) in PCa tissues compared with those in noncancerous prostate tissues. CCL18 upregulation was correlated with high Gleason score (P = 0.034) of patients with PCa. rCCL18 stimulation in PCa cells promoted cell migration and invasion but decreased DU145 cells apoptosis rate. Furthermore, subcutaneous homografts models showed the increased tumor growth and tumor vascularization with the CCL18 stimulation, and the expression of Ki67, PCNA, and CD31 in CCL18 stimulation mice was also significantly increased., Conclusions: Our data offer the convincing evidence that the upregulation of CCL18 may be involved in the malignant progression of PCa.