Modulation of CXCL14 (BRAK) expression in prostate cancer

BACKGROUND. Recent studies suggest inflammatory processes may be involved in the development or progression of prostate cancer. Chemokines are a family of cytokines that can play several roles in cancer progression including angiogenesis, inflammation, cell recruitment, and migration. METHODS. Real-time quantitative RT-PCR, in situ RNA hybridization, laser capture microscopy, immunohistochemistry, and cDNA array based technologies were used to examine CXCL14 (BRAK) expression in paired normal and tumor prostate. To determine the role CXCL14 expression has on cancer progression, LAPC4 cells were engineered to overexpress mouse or human CXCL14, and xenograft studies were performed. RESULTS. CXCL14 RNA expression was observed in normal and tumor prostate epithelium and focally in stromal cells adjacent to cancer. CXCL14 mRNA was significantly upregulated in localized prostate cancer and positively correlated with Gleason score. CXCL14 levels were unchanged in BPH specimens. LAPC4 cells expressing CXCL14 resulted in a 43% tumor growth inhibition (P = 0.019) in vivo compared to vector only xenografts. CONCLUSIONS. CXCL14 mRNA upregulation is a common feature in prostate cancer. The finding that CXCL14 expression inhibits tumor growth suggests this gene has tumor suppressive functions. (c) 2005 Wiley-Liss, Inc.