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 journalArticle

25 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

Fingerprint

Angiotensin Type 1 Receptor
Chemokine CCL2
Prostatic Neoplasms
Macrophages
Castration
Prostate-Specific Antigen
Phosphatidylinositol 3-Kinases
Recurrence
Neoplasm Grading
Renin-Angiotensin System
Angiotensin II
Neoplasms
Cell Line

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Regulation of monocyte chemoattractant protein-1 through angiotensin II type 1 receptor in prostate cancer. / Shirotake, Suguru; Miyajima, Akira; Kosaka, Takeo; Tanaka, Nobuyuki; Kikuchi, Eiji; Mikami, Shuji; Okada, Yasunori; Oya, Mototsugu.

In: American Journal of Pathology, Vol. 180, No. 3, 03.2012, p. 1008-1016.

Research output: Contribution to journalArticle

@article{6c51d196d4bd4ef1a0ee4194bb8e551f,
title = "Regulation of monocyte chemoattractant protein-1 through angiotensin II type 1 receptor in prostate cancer",
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.",
author = "Suguru Shirotake and Akira Miyajima and Takeo Kosaka and Nobuyuki Tanaka and Eiji Kikuchi and Shuji Mikami and Yasunori Okada and Mototsugu Oya",
year = "2012",
month = "3",
doi = "10.1016/j.ajpath.2011.11.027",
language = "English",
volume = "180",
pages = "1008--1016",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Regulation of monocyte chemoattractant protein-1 through angiotensin II type 1 receptor in prostate cancer

AU - Shirotake, Suguru

AU - Miyajima, Akira

AU - Kosaka, Takeo

AU - Tanaka, Nobuyuki

AU - Kikuchi, Eiji

AU - Mikami, Shuji

AU - Okada, Yasunori

AU - Oya, Mototsugu

PY - 2012/3

Y1 - 2012/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84857218019&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84857218019&partnerID=8YFLogxK

U2 - 10.1016/j.ajpath.2011.11.027

DO - 10.1016/j.ajpath.2011.11.027

M3 - Article

C2 - 22226738

AN - SCOPUS:84857218019

VL - 180

SP - 1008

EP - 1016

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 3

ER -