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Monocyte chemotactic protein‐1 (MCP‐1/CCL2) is associated with prostatic growth dysregulation and benign prostatic hyperplasia
Author(s) -
Fujita Kazutoshi,
Ewing Charles M.,
Getzenberg Robert H.,
Parsons J. Kellogg,
Isaacs William B.,
Pavlovich Christian P.
Publication year - 2009
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21081
Subject(s) - ccl2 , stromal cell , chemokine , monocyte , cytokine , prostate , biology , hyperplasia , inflammation , cancer research , medicine , immunology , endocrinology , cancer
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)‐1β, interferon‐γ, 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. Prostate 70: 473–481, 2010. © 2009 Wiley‐Liss, Inc.