Serum CXCL13 positively correlates with prostatic disease, prostate-specific antigen and mediates prostate cancer cell invasion, integrin clustering and cell adhesion.
Chemokines and their corresponding receptor interactions have been shown to be involved in prostate cancer (PCa) progression and organ-specific metastasis. We have recently shown that PCa cell lines and primary prostate tumors express CXCR5, which correlates with PCa grade. In this study, we present the first evidence that CXCL13, the only ligand for CXCR5, and IL-6 were significantly elevated in PCa patient serum compared to serum from subjects with benign prostatic hyperplasia (BPH), or high-grade prostatic intraepithelial neoplasia (HGPIN) as well as normal healthy donors (NHD). Serum CXCL13 levels significantly (p<0.0001) correlated with serum prostate-specific antigen (PSA), whereas serum IL-6 levels significantly (p<0.0003) correlated with CXCL13 serum levels. CXCL13 was found to be a better predictor of PCa than PSA. CXCL13 was highly expressed by human bone marrow endothelial (HBME) cells and osteoblasts (OBs), but not osteoclasts (OCs), following treatment with physiologically relevant levels of interleukin-6 (IL-6). We further demonstrate that CXCL13, produced by IL-6-treated HBME cells, was able to induce PCa cell invasion in a CXCR5-dependent manner. CXCL13-mediated PCa cell adhesion to HBME cells and alpha(v)beta(3)-integrin clustering was abrogated by CXCR5 blockade. These results demonstrate that the CXCL13-CXCR5 axis is significantly associated with PCa progression.
Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USA.
Shailesh
S
Singh
Rajesh
R
Singh
Praveen K
PK
Sharma
Udai P
UP
Singh
Shesh N
SN
Rai
Leland W K
LW
Chung
Carlton R
CR
Cooper
Kristian R
KR
Novakovic
William E
WE
Grizzle
James W
JW
Lillard
D014408:Biomarkers, Tumor / Q000097:blood; D001842:Bone and Bones / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D045744:Cell Line, Tumor; D054382:Chemokine CXCL13 / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood; D011470:Prostatic Hyperplasia / Q000097:blood / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000097:blood / Q000473:pathology; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology; D054380:Receptors, CXCR5 / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism
D014408:Biomarkers, Tumor; C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054382:Chemokine CXCL13; D016023:Integrins; D015850:Interleukin-6; D054380:Receptors, CXCR5; D017430:Prostate-Specific Antigen