Conclusions
Down regulation of CXCR7 protein by DHT and flagellin increased migration, supporting CXCR7 as decoy receptor counteracting CXCL12/CXCR4-mediated migration in prostate cancer cells.
Methods
Real-time PCR, western analysis, and migration assays were used to determine mRNA, protein, and functional changes, respectively.
Objective
To elucidate the regulation, function of the chemokine CXC-motif ligand 12 (CXCL12) and its receptors (CXCR) 4 and 7 in prostate cancer tumor microenvironment. Material: In-silico-analysis of expression in prostate cancer tissues. In-vitro comparison, testing of regulation in human prostate cancer cells LNCaP, DU145, and PC3. Treatment: Dihydrotestosterone (DHT) treatments (0-10 nM) were for 0-48 h. The inflammatory agent Flagellin treatment (20 ng/ml) was for 2 h. Migration assays were performed for 24 h using 10 ng/ml CXCL12.
Results
Malignant prostate cancer tissues exhibit higher CXCR4/7 mRNA ratio, and higher CXCR7 mRNA levels were detected in the androgen-responsive LNCaP cells. Putative androgen-responsive elements were identified in CXCR4, 7 gene, and exposure to DHT, flagellin increased CXCR4 mRNA but decreased CXCR7 mRNA levels in LNCaP cells. Androgen receptor siRNA significantly attenuated the effects of DHT on CXCR4, 7 mRNA in LNCaP cells. However, DHT and flagellin only decrease CXCR7 protein and additively increased migration of LNCaP cells towards CXCL12. Conclusions: Down regulation of CXCR7 protein by DHT and flagellin increased migration, supporting CXCR7 as decoy receptor counteracting CXCL12/CXCR4-mediated migration in prostate cancer cells.