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β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells
BACKGROUND: Chronic stress is well known to promote tumor progression, however, little is known whether chronic stress-mediated regulation of osteoblasts contributes to the migration and invasion of metastatic cancer cells. METHODS: The proliferation, migration and invasion of prostate cancer cells...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878637/ https://www.ncbi.nlm.nih.gov/pubmed/31771535 http://dx.doi.org/10.1186/s12885-019-6301-1 |
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author | Huang, Zhibin Li, Guihuan Zhang, Zhishuai Gu, Ruonan Wang, Wenyang Lai, Xiaoju Cui, Zhong-Kai Zeng, Fangyin Xu, Shiyuan Deng, Fan |
author_facet | Huang, Zhibin Li, Guihuan Zhang, Zhishuai Gu, Ruonan Wang, Wenyang Lai, Xiaoju Cui, Zhong-Kai Zeng, Fangyin Xu, Shiyuan Deng, Fan |
author_sort | Huang, Zhibin |
collection | PubMed |
description | BACKGROUND: Chronic stress is well known to promote tumor progression, however, little is known whether chronic stress-mediated regulation of osteoblasts contributes to the migration and invasion of metastatic cancer cells. METHODS: The proliferation, migration and invasion of prostate cancer cells were assessed by CCK-8 and transwell assay. HIF-1α expression of osteoblasts and epithelial-mesenchymal transition (EMT) markers of prostate cancer cells were examined by Western blot. The mRNA level of cytokines associated with bone metastasis in osteoblasts and EMT markers in PC-3 and DU145 cells were performed by qRT-PCR. Functional rescue experiment of cells were performed by using siRNA, plasmid transfection and inhibitor treatment. RESULTS: Isoproterenol (ISO), a pharmacological surrogate of sympathetic nerve activation induced by chronic stress, exhibited no direct effect on migration and invasion of PC-3 and DU145 prostate cancer cells. Whereas, osteoblasts pretreated with ISO promoted EMT, migration and invasion of PC-3 and DU145 cells, which could be inhibited by β2AR inhibitor. Mechanistically, ISO increased the secretion of CXCL12 via the β2AR-HIF-1α signaling in osteoblasts. Moreover, overexpression of HIF-1α osteoblasts promoted migration and invasion of PC-3 and DU145 cells, which was inhibited by addition of recombinant knockdown of CXCR4 in PC-3 and DU145 cells, and inhibiting CXCL12-CXCR4 signaling with LY2510924 blunted the effects of osteoblasts in response to ISO on EMT and migration as well as invasion of PC-3 and DU145 cells. CONCLUSIONS: These findings demonstrated that β2AR-HIF-1α-CXCL12 signaling in osteoblasts facilitates migration and invasion as well as EMT of prostate cancer cells, and may play a potential role in affecting bone metastasis of prostate cancer. |
format | Online Article Text |
id | pubmed-6878637 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-68786372019-11-29 β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells Huang, Zhibin Li, Guihuan Zhang, Zhishuai Gu, Ruonan Wang, Wenyang Lai, Xiaoju Cui, Zhong-Kai Zeng, Fangyin Xu, Shiyuan Deng, Fan BMC Cancer Research Article BACKGROUND: Chronic stress is well known to promote tumor progression, however, little is known whether chronic stress-mediated regulation of osteoblasts contributes to the migration and invasion of metastatic cancer cells. METHODS: The proliferation, migration and invasion of prostate cancer cells were assessed by CCK-8 and transwell assay. HIF-1α expression of osteoblasts and epithelial-mesenchymal transition (EMT) markers of prostate cancer cells were examined by Western blot. The mRNA level of cytokines associated with bone metastasis in osteoblasts and EMT markers in PC-3 and DU145 cells were performed by qRT-PCR. Functional rescue experiment of cells were performed by using siRNA, plasmid transfection and inhibitor treatment. RESULTS: Isoproterenol (ISO), a pharmacological surrogate of sympathetic nerve activation induced by chronic stress, exhibited no direct effect on migration and invasion of PC-3 and DU145 prostate cancer cells. Whereas, osteoblasts pretreated with ISO promoted EMT, migration and invasion of PC-3 and DU145 cells, which could be inhibited by β2AR inhibitor. Mechanistically, ISO increased the secretion of CXCL12 via the β2AR-HIF-1α signaling in osteoblasts. Moreover, overexpression of HIF-1α osteoblasts promoted migration and invasion of PC-3 and DU145 cells, which was inhibited by addition of recombinant knockdown of CXCR4 in PC-3 and DU145 cells, and inhibiting CXCL12-CXCR4 signaling with LY2510924 blunted the effects of osteoblasts in response to ISO on EMT and migration as well as invasion of PC-3 and DU145 cells. CONCLUSIONS: These findings demonstrated that β2AR-HIF-1α-CXCL12 signaling in osteoblasts facilitates migration and invasion as well as EMT of prostate cancer cells, and may play a potential role in affecting bone metastasis of prostate cancer. BioMed Central 2019-11-26 /pmc/articles/PMC6878637/ /pubmed/31771535 http://dx.doi.org/10.1186/s12885-019-6301-1 Text en © The Author(s). 2019 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 Article Huang, Zhibin Li, Guihuan Zhang, Zhishuai Gu, Ruonan Wang, Wenyang Lai, Xiaoju Cui, Zhong-Kai Zeng, Fangyin Xu, Shiyuan Deng, Fan β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells |
title | β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells |
title_full | β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells |
title_fullStr | β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells |
title_full_unstemmed | β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells |
title_short | β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells |
title_sort | β2ar-hif-1α-cxcl12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878637/ https://www.ncbi.nlm.nih.gov/pubmed/31771535 http://dx.doi.org/10.1186/s12885-019-6301-1 |
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