Regulation of monocyte chemoattractant protein-1 through angiotensin II type 1 receptor in prostate cancer

Suguru Shirotake, Akira Miyajima, Takeo Kosaka, Nobuyuki Tanaka, Eiji Kikuchi, Shuji Mikami, Yasunori Okada, Mototsugu Oya

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1008-1016
Number of pages9
JournalAmerican Journal of Pathology
Volume180
Issue number3
DOIs
Publication statusPublished - 2012 Mar

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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