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Cited by 62Immune cells in cancerMesenchymal stem cell researchCancer Cells and Metastasis

Activation of mesenchymal stem cells by macrophages promotes tumor progression through immune suppressive effects

Open access
Jia, Xiao-hua, Feng, Guo-wei, Wang, Zhong-liang, Du, Yang, Shen, Chen, Hui, Hui, Peng, Dong, Li, Zong-jin +2 more·2016·Oncotarget
DOI 10.18632/oncotarget.8064PMC PMC4991502
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Abstract

// Xiao-hua Jia 1 , Guo-wei Feng 2, 4, 5 , Zhong-liang Wang 3 , Yang Du 1 , Chen Shen 1 , Hui Hui 1 , Dong Peng 1, 3 , Zong-jin Li 4 , De-ling Kong 5 , Jie Tian 1, 6 1 Key Laboratory of Molecular Imaging of the Chinese Academy of Sciences, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China 2 Department of Genitourinary Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China 3 School of Life Science and Technology, Xidian University, Shaanxi, Xi’an 710071, China 4 Department of Pathophysiology, Nankai University School of Medicine, Tianjin 300071, China 5 State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China 6 Beijing Key Laboratory of Molecular Imaging, Beijing 100190, China Correspondence to: Jie Tian, e-mail: Jie.tian@ia.ac.cn Keywords: mesenchymal stem cells, macrophages, inflammation, cancer, MCP1 Received: October 02, 2015 Accepted: January 23, 2016 Published: March 14, 2016 ABSTRACT Cancer development and progression is linked to tumor-associated macrophages (TAMs). Distinct TAMs subsets perform either protective or pathogenic effects in cancer. A protective role in carcinogenesis has been described for M1 macrophages, which activate antitumor mechanisms. By comparison, TAMs isolated from solid and metastatic tumors have a suppressive M2-like phenotype, which could support multiple aspects of tumor progression. Currently, it has not been clearly understood how macrophages in tumor-associated stroma could be hijacked to support tumor growth. Mesenchymal stem cells (MSCs) actively interact with components of the innate immune system and display both anti-inflammatory and pro-inflammatory effects. Here, we tested whether MSCs could favor the tumor to escape from immunologic surveillance in the presence of M1 macrophages. We found that MSCs educated by M1 condition medium (cMSCs) possessed a greatly enhanced ability in promoting tumor growth in vivo . Examination of cytokines/chemokines showed that the cMSCs acquired a regulatory profile, which expressed high levels of iNOS and MCP1. Consistent with an elevated MCP1 expression in cMSCs, the tumor-promoting effect of the cMSCs depended on MCP1 mediated macrophage recruitment to tumor sites. Furthermore, IL-6 secreted by the cMSCs could polarize infiltrated TAMs into M2-like macrophages. Therefore, when macrophages changed into M1 pro-inflammation type in tumor microenvironment, the MSCs would act as poor sensors and switchers to accelerate tumor growth.

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  • MSCs can promote the polarization of TAMs towards the M2 phenotype by secreting IL-6.

    “Furthermore, MSCs can promote the polarization of TAMs towards the M2 phenotype by secreting IL-6 [49].”

    From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [49]

    The Results section reports that IL-6 from M1-conditioned MSCs (cMSCs) contributes to polarization of TAMs into M2-like macrophages; blocking IL-6 reduced M2-associated markers. The citing sentence omits the conditioning and describes the outcome as an M2 phenotype rather than the M2-like phenotype observed in the study. (LLM, conf=0.83)

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Authors
Jia, X.-H., Feng, G.-W., Wang, Z.-L., Du, Y., Shen, C., Hui, H., Peng, D., Li, Z.-J., Kong, D.-L., & Tian, J.
Affiliations
  • Chinese Academy of Sciences (CN)
  • Department of Genitourinary Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
  • School of Life Science and Technology, Xidian University, Shaanxi, Xi'an 710071, China
  • Xidian University (CN)
  • Department of Pathophysiology, Nankai University School of Medicine, Tianjin 300071, China
  • State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China
Corresponding author
Tian, Jie
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2016-03-14
Volume
7
Issue
15
Pages
20934-20944
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.8064
PMC
PMC4991502
OpenAlex
W2329962575
Cited by
62
References
4
Citations by year
2026: 1 · 2025: 6 · 2024: 3 · 2023: 7 · 2022: 13 · 2021: 4 · 2020: 6 · 2019: 7 · 2018: 4 · 2017: 5 · 2016: 6
FWCI
4.45
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81227901, 61231004, 81470083, 61231004, 81,227,901)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
mesenchymal stem cells, tumor-associated macrophages, M1 macrophages, M2 macrophages, tumor progression, immunosuppression, tumor microenvironment, MCP-1, tumor immunosuppression, macrophage polarization, tumor stroma, tumor immunology, metastasis, cell adhesion
MeSH terms
Animals, Breast Neoplasms, Cell Transformation, Neoplastic, Female, Glioblastoma, Carcinoma, Hepatocellular, Humans, Immunosuppression Therapy, Liver Neoplasms, Macrophages, Mice, Inbred C57BL, Mice, Nude, Tumor Cells, Cultured, Interleukin-6, Cytokines, Culture Media, Conditioned, Apoptosis, Chemokines, Xenograft Model Antitumor Assays, Cell Proliferation, Mice, Tumor Microenvironment, Mesenchymal Stem Cells

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