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Endothelial cells promote metastasis of prostate cancer by enhancing autophagy
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 r...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131784/ https://www.ncbi.nlm.nih.gov/pubmed/30200999 http://dx.doi.org/10.1186/s13046-018-0884-2 |
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author | Zhao, Ruizhe Bei, Xiaoyu Yang, Boyu Wang, Xiaohai Jiang, Chenyi Shi, Fei Wang, Xingjie Zhu, Yiping Jing, Yifeng Han, Bangmin Xia, Shujie Jiang, Qi |
author_facet | Zhao, Ruizhe Bei, Xiaoyu Yang, Boyu Wang, Xiaohai Jiang, Chenyi Shi, Fei Wang, Xingjie Zhu, Yiping Jing, Yifeng Han, Bangmin Xia, Shujie Jiang, Qi |
author_sort | Zhao, Ruizhe |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-018-0884-2) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6131784 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-61317842018-09-13 Endothelial cells promote metastasis of prostate cancer by enhancing autophagy Zhao, Ruizhe Bei, Xiaoyu Yang, Boyu Wang, Xiaohai Jiang, Chenyi Shi, Fei Wang, Xingjie Zhu, Yiping Jing, Yifeng Han, Bangmin Xia, Shujie Jiang, Qi J Exp Clin Cancer Res Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-018-0884-2) contains supplementary material, which is available to authorized users. BioMed Central 2018-09-10 /pmc/articles/PMC6131784/ /pubmed/30200999 http://dx.doi.org/10.1186/s13046-018-0884-2 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Zhao, Ruizhe Bei, Xiaoyu Yang, Boyu Wang, Xiaohai Jiang, Chenyi Shi, Fei Wang, Xingjie Zhu, Yiping Jing, Yifeng Han, Bangmin Xia, Shujie Jiang, Qi Endothelial cells promote metastasis of prostate cancer by enhancing autophagy |
title | Endothelial cells promote metastasis of prostate cancer by enhancing autophagy |
title_full | Endothelial cells promote metastasis of prostate cancer by enhancing autophagy |
title_fullStr | Endothelial cells promote metastasis of prostate cancer by enhancing autophagy |
title_full_unstemmed | Endothelial cells promote metastasis of prostate cancer by enhancing autophagy |
title_short | Endothelial cells promote metastasis of prostate cancer by enhancing autophagy |
title_sort | endothelial cells promote metastasis of prostate cancer by enhancing autophagy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131784/ https://www.ncbi.nlm.nih.gov/pubmed/30200999 http://dx.doi.org/10.1186/s13046-018-0884-2 |
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