Cargando…

Zoledronic acid prevents the tumor-promoting effects of mesenchymal stem cells via MCP-1 dependent recruitment of macrophages

Zoledronic acid (ZA) has been tested in clinical trials as an additive therapy for early-stage breast cancer. However, the mechanism by which ZA exerts its antitumor activity is still unclear. The aim of this study is to investigate whether the prevention of tumor growth by ZA is through regulating...

Descripción completa

Detalles Bibliográficos
Autores principales: Jia, Xiao-Hua, Du, Yang, Mao, Duo, Wang, Zhong-Liang, He, Zhen-Qiang, Qiu, Jing-Dan, Ma, Xi-Bo, Shang, Wen-Ting, Ding, Dan, Tian, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694882/
https://www.ncbi.nlm.nih.gov/pubmed/26305552
_version_ 1782407544647450624
author Jia, Xiao-Hua
Du, Yang
Mao, Duo
Wang, Zhong-Liang
He, Zhen-Qiang
Qiu, Jing-Dan
Ma, Xi-Bo
Shang, Wen-Ting
Ding, Dan
Tian, Jie
author_facet Jia, Xiao-Hua
Du, Yang
Mao, Duo
Wang, Zhong-Liang
He, Zhen-Qiang
Qiu, Jing-Dan
Ma, Xi-Bo
Shang, Wen-Ting
Ding, Dan
Tian, Jie
author_sort Jia, Xiao-Hua
collection PubMed
description Zoledronic acid (ZA) has been tested in clinical trials as an additive therapy for early-stage breast cancer. However, the mechanism by which ZA exerts its antitumor activity is still unclear. The aim of this study is to investigate whether the prevention of tumor growth by ZA is through regulating the mesenchymal stem cells (MSC)-monocyte chemotactic protein 1 (MCP-1)-macrophages axis in the tumor microenvironment. To address this issue, MDA-MB-231-FLUC human breast cancer cells were cultured and injected either alone, or coupled with MSC into the mammary fat pads of nude mice. MSC were treated with either ZA or untreated. Tumor growth was determined by using an in vivo bioluminescence imaging (BLI) and the tumor-associated macrophages (TAMs) in tumor tissues were immunohistochemically analyzed by using CD206 antibody. The effects of ZA on the cytokine related gene expression of MSC were assessed by using real-time PCR. In this study, we found that ZA-treated mice showed a significant delay in tumor growth. In addition, our data revealed that ZA weakened the ability of MSC to promote tumor growth by impairing TAMs recruitment and tumor vascularization. Furthermore, it was found that ZA decreased MCP-1 expression of MSC, and therefore reduced the recruitment of TAMs to the tumor sites and hence inhibited the tumor growth. Altogether, our study demonstrated ZA can prevent the tumor-promoting effects of MSC. The antitumor effects of ZA were caused by decreasing the MCP-1 expression of MSC, which further decreased the infiltration of TAMs into tumor sites, and therefore inhibited the tumor growth.
format Online
Article
Text
id pubmed-4694882
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-46948822016-01-20 Zoledronic acid prevents the tumor-promoting effects of mesenchymal stem cells via MCP-1 dependent recruitment of macrophages Jia, Xiao-Hua Du, Yang Mao, Duo Wang, Zhong-Liang He, Zhen-Qiang Qiu, Jing-Dan Ma, Xi-Bo Shang, Wen-Ting Ding, Dan Tian, Jie Oncotarget Research Paper Zoledronic acid (ZA) has been tested in clinical trials as an additive therapy for early-stage breast cancer. However, the mechanism by which ZA exerts its antitumor activity is still unclear. The aim of this study is to investigate whether the prevention of tumor growth by ZA is through regulating the mesenchymal stem cells (MSC)-monocyte chemotactic protein 1 (MCP-1)-macrophages axis in the tumor microenvironment. To address this issue, MDA-MB-231-FLUC human breast cancer cells were cultured and injected either alone, or coupled with MSC into the mammary fat pads of nude mice. MSC were treated with either ZA or untreated. Tumor growth was determined by using an in vivo bioluminescence imaging (BLI) and the tumor-associated macrophages (TAMs) in tumor tissues were immunohistochemically analyzed by using CD206 antibody. The effects of ZA on the cytokine related gene expression of MSC were assessed by using real-time PCR. In this study, we found that ZA-treated mice showed a significant delay in tumor growth. In addition, our data revealed that ZA weakened the ability of MSC to promote tumor growth by impairing TAMs recruitment and tumor vascularization. Furthermore, it was found that ZA decreased MCP-1 expression of MSC, and therefore reduced the recruitment of TAMs to the tumor sites and hence inhibited the tumor growth. Altogether, our study demonstrated ZA can prevent the tumor-promoting effects of MSC. The antitumor effects of ZA were caused by decreasing the MCP-1 expression of MSC, which further decreased the infiltration of TAMs into tumor sites, and therefore inhibited the tumor growth. Impact Journals LLC 2015-08-03 /pmc/articles/PMC4694882/ /pubmed/26305552 Text en Copyright: © 2015 Jia et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Jia, Xiao-Hua
Du, Yang
Mao, Duo
Wang, Zhong-Liang
He, Zhen-Qiang
Qiu, Jing-Dan
Ma, Xi-Bo
Shang, Wen-Ting
Ding, Dan
Tian, Jie
Zoledronic acid prevents the tumor-promoting effects of mesenchymal stem cells via MCP-1 dependent recruitment of macrophages
title Zoledronic acid prevents the tumor-promoting effects of mesenchymal stem cells via MCP-1 dependent recruitment of macrophages
title_full Zoledronic acid prevents the tumor-promoting effects of mesenchymal stem cells via MCP-1 dependent recruitment of macrophages
title_fullStr Zoledronic acid prevents the tumor-promoting effects of mesenchymal stem cells via MCP-1 dependent recruitment of macrophages
title_full_unstemmed Zoledronic acid prevents the tumor-promoting effects of mesenchymal stem cells via MCP-1 dependent recruitment of macrophages
title_short Zoledronic acid prevents the tumor-promoting effects of mesenchymal stem cells via MCP-1 dependent recruitment of macrophages
title_sort zoledronic acid prevents the tumor-promoting effects of mesenchymal stem cells via mcp-1 dependent recruitment of macrophages
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694882/
https://www.ncbi.nlm.nih.gov/pubmed/26305552
work_keys_str_mv AT jiaxiaohua zoledronicacidpreventsthetumorpromotingeffectsofmesenchymalstemcellsviamcp1dependentrecruitmentofmacrophages
AT duyang zoledronicacidpreventsthetumorpromotingeffectsofmesenchymalstemcellsviamcp1dependentrecruitmentofmacrophages
AT maoduo zoledronicacidpreventsthetumorpromotingeffectsofmesenchymalstemcellsviamcp1dependentrecruitmentofmacrophages
AT wangzhongliang zoledronicacidpreventsthetumorpromotingeffectsofmesenchymalstemcellsviamcp1dependentrecruitmentofmacrophages
AT hezhenqiang zoledronicacidpreventsthetumorpromotingeffectsofmesenchymalstemcellsviamcp1dependentrecruitmentofmacrophages
AT qiujingdan zoledronicacidpreventsthetumorpromotingeffectsofmesenchymalstemcellsviamcp1dependentrecruitmentofmacrophages
AT maxibo zoledronicacidpreventsthetumorpromotingeffectsofmesenchymalstemcellsviamcp1dependentrecruitmentofmacrophages
AT shangwenting zoledronicacidpreventsthetumorpromotingeffectsofmesenchymalstemcellsviamcp1dependentrecruitmentofmacrophages
AT dingdan zoledronicacidpreventsthetumorpromotingeffectsofmesenchymalstemcellsviamcp1dependentrecruitmentofmacrophages
AT tianjie zoledronicacidpreventsthetumorpromotingeffectsofmesenchymalstemcellsviamcp1dependentrecruitmentofmacrophages