Monocyte chemoattractant protein-1 (MCP-1/CCL2) is reported to contribute to tumor progression and is regulated by the renin-angiotensin system in hypertensive disease.
In this study, we investigated the clinical outcome of MCP-1 expression in patients with prostate cancer (CaP) and the regulation of MCP-1 through angiotensin II (AngII) type 1 receptor (AT1R) in CaP. Specimens were obtained from 138 CaP patients and analyzed by immunostaining for both MCP-1 and macrophages. We investigated the regulation of MCP-1 expression through AT1R both in vivo and in vitro using three human prostate cancer cell lines: LNCaP, C4-2, and C4-2AT6. Specimens with a high Gleason score (≥7) and a high pathological classification (≤pT3), and those with castration-resistant prostate cancer showed significantly higher MCP-1 expression and higher macrophage infiltration than low malignant potential CaP. High MCP-1 expression in CaP correlated significantly with high prostate-specific antigen (PSA) recurrence rates. AngII induced significantly higher MCP-1 levels in C4-2AT6 than in LNCaP, whereas AT1R blockade (ARB) inhibited MCP-1 production via the inhibition of the PI3K/Akt pathway in C4-2AT6. ARB also significantly suppressed MCP-1 expression in C4-2AT6 tumors. Our study is the first to demonstrate that both high MCP-1 expression and high macrophage infiltration in CaP specimens correlate with a high PSA recurrence rate and that ARB inhibits MCP-1 expression through the PI3K/Akt pathway and blocks macrophage infiltration in castration-resistant prostate cancer.
Written by:
Shirotake S, Miyajima A, Kosaka T, Tanaka N, Kikuchi E, Mikami S, Okada Y, Oya M. Are you the author?
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Reference: Am J Pathol. 2012 Mar;180(3):1008-16. Epub 2012 Jan 6.
PubMed Abstract
PMID: 22226738
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