Chemokines and chemokine receptors have been shown to be involved in metastatic process of prostate cancer (PCa). In this study, we show primary PCa tissues and cell lines (LNCaP and PC3) express CXCR5, a specific chemokine receptor for CXCL13. Expression of CXCR5 was significantly higher (p < 0.001) in PCa cases than compared to normal match (NM) tissues. CXCR5 intensity correlated (R2 = 0.97) with Gleason score. While prostate tumor tissues with Gleason scores ≥ 7, displayed predominantly nuclear CXCR5 expression patterns, PCa specimens with Gleason scores ≤ 6 showed predominantly membrane and cytoplasmic expression patterns that were comparable to benign prostatic hyperplasia (BPH). Similar to tissue expression, PCa cell lines expressed significantly more CXCR5 than normal prostatic epithelial cells (PrECs), and CXCR5 expression was distributed among intracellular and extracellular compartments. Functional in vitro assays showed higher migratory and invasive potentials toward CXCL13, an effect that was mediated by CXCR5. In both PCa cell lines, CXCL13 treatment increased the expression of collagenase-1 or matrix metalloproteinase-1 (MMP-1), collagenase-3 (MMP-13), stromelysin-1 (MMP-3), stromelysin-2 (MMP-10) and stromelysin-3 (MMP-11). These data demonstrate the clinical and biological relevance of the CXCL13-CXCR5 pathway and its role in PCa cell invasion and migration. © 2009 UICC.