Targeting TR4 nuclear receptor suppresses prostate cancer invasion via reduction of infiltrating macrophages with alteration of the TIMP-1/MMP2/MMP9 signals
Authors: Gonghui Li
Bide Chen
Xianfan Ding
Chawnshang Chang
Liqun Xia
Dong-Rong Yang
Yuanjie Niu
Shicheng Yu
Mingchao Wang
Journal: Molecular Cancer (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: TR4; macrophages; PCa; metastasis; invasion
Affiliations: Department of Urology and Chawnshang Chang Liver Cancer Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China. ., George Whipple Lab for Cancer Research, Departments of Pathology, Urology and Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, 14646, USA. ., Department of Urology, the 2nd Affiliated Hospital of Soochow University, Suzhou, 215004, China. ., Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, Tianjin Medical University, Tianjin, 300211, China. ., Sex Hormone Research Center, China Medical University/Hospital, Taichung, 404, Taiwan. .

Abstract:  Background: TR4 nuclear receptor 4 (TR4) plays an important role in macrophages-associated foam cell formation of cardiovascular diseases and infiltrating macrophages are critical for prostate cancer (PCa) progression. However, the linkage of macrophages and TR4 and their impacts on PCa metastasis remains unclear. Results: Knocking-down TR4 in human PCa cells (C4-2, CWR22Rv1), but not in human macrophages cells (THP-1), led to suppress the macrophages infiltration to PCa cells. The consequences of such suppression of the recruitment of macrophages toward PCa then resulted in suppressing the PCa cell invasion. Mechanism dissection found that knocking-down TR4 in PCa cells suppressed metastasis-related genes including MMP2, with induction of TIMP-1. Interruption assays using TIMP-1 neutralizing antibody could then reverse TR4-macrophage-mediated PCa invasion. IHC staining showed higher TR4 level, more macrophage infiltration, lower TIMP-1 and stronger MMP2/MMP9 in tumor tissues of the Gleason score 5 + 4 patients compared with the Gleason score 3 + 3 patients. Conclusion: Targeting TR4 in prostate tumor microenvironment might represent a potential new therapeutic approach to better battle PCa metastasis. 

Retracted: No

PubPeer comments:
 Figure 2A. * Red boxes: Two panels representing different experiments appear to show an overlap. ![file] , 
 2020 correction found here: https: molecular-cancer.biomedcentral.com articles 10.1186 s12943-020-01212-7  *Following the publication of the original article [1], the corresponding author recently found error in the Fig. 2A. Below is the corrected image. This error could be due to mislabel and or incorrect insertion during transfer of numerous images between computers in two countries after he returned from USA and became occupied with his university work to establish a laboratory. They assure that the correction of this image will not alter the conclusion of the results. The authors are appreciative for the publication of this correction paper. * I am not sure if the statement  the corresponding author recently found error is correct, though. I reported the duplication to the journal and here on PubPeer. ,