Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.4658
Title: Zoledronic acid prevents the tumor-promoting effects of mesenchymal stem cells via MCP-1 dependent recruitment of macrophages
Authors: Jia, X.-H
Du, Y
Mao, D 
Wang, Z.-L
He, Z.-Q
Qiu, J.-D
Ma, X.-B
Shang, W.-T
Ding, D
Tian, J
Keywords: 5' nucleotidase
beta1 integrin
CD206 antigen
cell surface marker
endoglin
monocyte chemotactic protein 1
Thy 1 antigen
unclassified drug
zoledronic acid
bisphosphonic acid derivative
bone density conservation agent
cell surface receptor
cytokine
imidazole derivative
lectin
luciferase
mannose binding lectin
mannose receptor
monocyte chemotactic protein 1
zoledronic acid
animal cell
animal experiment
animal model
animal tissue
antiangiogenic activity
Article
breast cancer cell line
breast tumor
cancer inhibition
controlled study
female
gene expression
human
human cell
macrophage migration inhibition
male
mammary gland fat
mesenchymal stem cell
mouse
nonhuman
tumor associated leukocyte
tumor microenvironment
animal
Breast Neoplasms
C57BL mouse
cell culture
drug effects
drug screening
gene expression regulation
genetics
immunohistochemistry
luminescence
macrophage
Mammary Neoplasms, Experimental
mesenchymal stem cell transplantation
mesenchymal stroma cell
metabolism
nude mouse
procedures
reverse transcription polymerase chain reaction
RNA interference
tumor cell line
tumor volume
Animals
Bone Density Conservation Agents
Breast Neoplasms
Cell Line, Tumor
Cells, Cultured
Chemokine CCL2
Cytokines
Diphosphonates
Gene Expression Regulation, Neoplastic
Humans
Imidazoles
Immunohistochemistry
Lectins, C-Type
Luciferases
Luminescent Measurements
Macrophages
Mammary Neoplasms, Experimental
Mannose-Binding Lectins
Mesenchymal Stem Cell Transplantation
Mesenchymal Stromal Cells
Mice, Inbred C57BL
Mice, Nude
Receptors, Cell Surface
Reverse Transcriptase Polymerase Chain Reaction
RNA Interference
Tumor Burden
Xenograft Model Antitumor Assays
Issue Date: 2015
Citation: Jia, X.-H, Du, Y, Mao, D, Wang, Z.-L, He, Z.-Q, Qiu, J.-D, Ma, X.-B, Shang, W.-T, Ding, D, Tian, J (2015). Zoledronic acid prevents the tumor-promoting effects of mesenchymal stem cells via MCP-1 dependent recruitment of macrophages. Oncotarget 6 (28) : 26018-26028. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.4658
Rights: Attribution 4.0 International
Abstract: 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 tumorassociated 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.
Source Title: Oncotarget
URI: https://scholarbank.nus.edu.sg/handle/10635/180936
ISSN: 19492553
DOI: 10.18632/oncotarget.4658
Rights: Attribution 4.0 International
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