J.W. Lillard Jr.

Associate Dean for Research, Director Cancer Research Program, Director of the Office for Translational Technologies, Professor of Microbiology, Biochemistry, & Immunology, Morehouse School of Medicine, 720 Westivew Drive SW, Atlanta, GA 30310, USA

Abstract:

We have recently reported, chemokine receptor CXCR5 and its ligand CXCL13 expression correlates with prostate tumor staging. We have noted differential expression of CXCR5 by prostate cancer (PCa) cell lines. By virtue of the presence of elevated CXCL13 in patient serum, bone marrow endothelium, and CXCR5 expression on the surface of PCa cells, we hypothesized that gradient-dependent CXCR5-CXCL13 interactions are responsible in part for PCa cell bone metastases and inhibition of this axis may prove beneficial for prevention of bone metastasis and tumor progression. To test this hypothesis, luciferase-expressing PC3 cells were injected into the right carotid artery or into the tibia of nude mice. Before and after the development of bone metastases, groups were treated with control or anti-CXCL13 antibody every third day and monitored for tumor progression or regression by non-invasive bioluminescent and microCT in vivo imaging. We demonstrate CXCL13 is present in bone marrow of tumor-bearing mice following intra-cardiac /intra-tibial injection. Finally, CXCL13 blockade significantly delayed prostate tumor formation, osteolysis, and spread to bones as well as regressed tibial prostate tumors. Our study shows that the CXCL13-CXCR5 axis supports PCa bone metastasis and growth and provides the rationale to develop this antibody therapy for clinic use.

Grant Support: G12 RR03034, U54 CA118638 and P60MD00525.