Monocyte chemotactic protein-1 (MCP-1/CCL2) is associated with prostatic growth dysregulation and benign prostatic hyperplasia.
BACKGROUND
Chronic inflammation is commonly observed in benign prostate hyperplasia (BPH), and prostate tissue often contains increased inflammatory infiltrates, including T cells and macrophages. Cytokines are not only key mediators of inflammation but may also play important roles in the initiation and progression of BPH.


METHODS
In order to determine what cytokines might be involved in prostatic enlargement, expressed prostatic secretions (EPS) from ex vivo prostates were analyzed by human cytokine antibody microarray and ELISA. Prostate epithelial cells (PrEC) and prostate stromal cells (PrSC) were used for ELISA, proliferation, and Western blot assays.


RESULTS
Monocyte chemotactic protein-1 (MCP-1/CCL2) was one of the most elevated proteins in secretions from large prostate glands. PrSC were found to secrete MCP-1; Western blotting showed that both PrSC and PrEC express the MCP-1 receptor CCR2 which by RT-PCR was the CCR2b isoform. Proliferation assays showed that MCP-1 stimulates the proliferation of PrEC, but not PrSC, and that a specific MCP-1 antagonist (RS102895) suppressed this effect. Conditioned medium from PrSC stimulated the proliferation of PrEC as well, an effect completely inhibited by both RS102895 and a neutralizing anti-MCP-1 monoclonal antibody. The inflammatory cytokines interleukin (IL)-1 beta, interferon-gamma, and IL-2 enhanced the secretion of MCP-1 from PrEC and PrSC. In addition, MCP-1 levels in EPS correlated with mRNA levels of the macrophage marker CD68 in the same secretions.


CONCLUSIONS
The cytokine MCP-1, of apparent prostatic stromal cell origin, may play an important role in prostatic enlargement and BPH, and is a candidate biomarker for these pathologic processes.
Fujita
Kazutoshi
K
The Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21218, USA.
Ewing
Charles M
CM
Getzenberg
Robert H
RH
Parsons
J Kellogg
JK
Isaacs
William B
WB
Pavlovich
Christian P
CP
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000032:analysis / Q000502:physiology*; D016207:Cytokines / Q000032:analysis; D006801:Humans; D008297:Male; D011467:Prostate / Q000473:pathology*; D011470:Prostatic Hyperplasia / Q000209:etiology*; D017154:Stromal Cells / Q000378:metabolism
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines