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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2018 | Research

Endothelial cells promote metastasis of prostate cancer by enhancing autophagy

Authors: Ruizhe Zhao, Xiaoyu Bei, Boyu Yang, Xiaohai Wang, Chenyi Jiang, Fei Shi, Xingjie Wang, Yiping Zhu, Yifeng Jing, Bangmin Han, Shujie Xia, Qi Jiang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

Abstract

Background

Prostate cancer is one of the most common malignancies. Increasing evidence suggested that endothelial cells may contribute to prostate cancer progression and metastasis. Most recently, autophagy has been proposed to plays a significant role in tumorigenesis and metastasis. Also, it is reported that downregulation of androgen receptor (AR) induces autophagy in prostate cancer cells. However, the underlying mechanisms remain unclear. Here, we aim to explore the role and mechanisms of endothelial cell in prostate cancer progression.

Methods

The coculture system was established to test the effect of endothelial cells on prostate cancer cells. We performed antibody array and ELISA were used to profile the cytokine expression pattern of endothelial cells in supernatant. Western blot and RT-PCR were used to determine the mechanism by endothelial cells to promote invasion ability of prostate cancer cells. Maraviroc and chloroquine were used to block the CCL5/CCR5 and autophagy pathway respectively. Orthotopic xenograft mouse models and drug treatment study were conducted to determine the role of endothelial cells in promoting metastatic potential in vivo.

Results

We use CPRC prostate cancer model and demonstrate that endothelial cells secrete large amount of CCL5 and induces autophagy by suppressing AR expression in prostate cancer cell lines. Consequently, elevated autophagy accelerates focal adhesions proteins disassembly and promoted prostate cancer invasion. Inhibition of both CCL5/CCR5 signaling and autophagy significantly reduces metastasis in vivo.

Conclusions

Together, our data establish the function for endothelial cells in tumor metastasis and propose new drug target for mCRPC.

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Title: Endothelial cells promote metastasis of prostate cancer by enhancing autophagy
Authors: Ruizhe Zhao
Xiaoyu Bei
Boyu Yang
Xiaohai Wang
Chenyi Jiang
Fei Shi
Xingjie Wang
Yiping Zhu
Yifeng Jing
Bangmin Han
Shujie Xia
Qi Jiang
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-018-0884-2

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Abstract

Background

Methods

Results

Conclusions

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