Myeloid-Derived Suppressor Cells Promote Metastasis in Breast Cancer After the Stress of Operative Removal of the Primary Cancer

Objective: To investigate the role of myeloid-derived suppressor cells (MDSC) in cancer progression after the stress of operative removal and the potential treatment value of MDSC depletion.Summary Background Data: Surgery is the most important treatment strategy in breast cancer. Recent research ha...

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Main Authors: Xuelei Ma, Manni Wang, Tao Yin, Yunuo Zhao, Xiawei Wei
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-09-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fonc.2019.00855/full
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author Xuelei Ma
Manni Wang
Tao Yin
Yunuo Zhao
Xiawei Wei
author_facet Xuelei Ma
Manni Wang
Tao Yin
Yunuo Zhao
Xiawei Wei
author_sort Xuelei Ma
collection DOAJ
description Objective: To investigate the role of myeloid-derived suppressor cells (MDSC) in cancer progression after the stress of operative removal and the potential treatment value of MDSC depletion.Summary Background Data: Surgery is the most important treatment strategy in breast cancer. Recent research has provided evidence that operations may promote cancer metastases under some circumstances.Methods: A mouse model of breast cancer (administration of the murine breast cancer 4T1 cells subcutaneously) and the stress of operation were used to compare immune responses and survival outcomes. Flow cytometry was performed to detect the expression of CD11b and Gr1 MDSCs in tumor tissues and lung metastases. Cytokine levels were detected with three-color flow cytometry and enzyme-linked immunosorbent assay (ELISA). MDSCs were isolated and co-cultured with 4T1 cells to identify any morphological change with immunofluorescence. The anti Gr-1 antibody was used to detect the function of the anti-Gr1 treatment in breast cancer.Results: The operative stress impaired the overall survival, leading to an increased number of MDSCs that preferentially infiltrated the tumor microenvironment and promoted tumor metastasis. In both in vitro and in vivo assays, MDSCs induced the epithelial-mesenchymal transition (EMT) of tumor cells through the up-regulation of TGF-beta1, VEGF, and IL-10. Furthermore, a treatment strategy of MDSC depletion was found to reduce pulmonary metastases after operations.Conclusions: The stress of operation could impair the overall survival in mice. The infiltrated MDSCs appear to induce EMT of tumor cells and increase metastases through the up-regulation of TGF-beta1, VEGF, and IL-10 levels. MDSC depletion could be a promising treatment strategy to prevent immune evasion after operations.
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spelling doaj.art-fa18e325738a4f3498c7079eae9450a12022-12-21T18:31:20ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-09-01910.3389/fonc.2019.00855465673Myeloid-Derived Suppressor Cells Promote Metastasis in Breast Cancer After the Stress of Operative Removal of the Primary CancerXuelei Ma0Manni Wang1Tao Yin2Yunuo Zhao3Xiawei Wei4State Key Laboratory of Biotherapy, Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, ChinaState Key Laboratory of Biotherapy, Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, ChinaState Key Laboratory of Biotherapy, Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, ChinaState Key Laboratory of Biotherapy, Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, ChinaLab of Aging Research and Nanotoxicology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaObjective: To investigate the role of myeloid-derived suppressor cells (MDSC) in cancer progression after the stress of operative removal and the potential treatment value of MDSC depletion.Summary Background Data: Surgery is the most important treatment strategy in breast cancer. Recent research has provided evidence that operations may promote cancer metastases under some circumstances.Methods: A mouse model of breast cancer (administration of the murine breast cancer 4T1 cells subcutaneously) and the stress of operation were used to compare immune responses and survival outcomes. Flow cytometry was performed to detect the expression of CD11b and Gr1 MDSCs in tumor tissues and lung metastases. Cytokine levels were detected with three-color flow cytometry and enzyme-linked immunosorbent assay (ELISA). MDSCs were isolated and co-cultured with 4T1 cells to identify any morphological change with immunofluorescence. The anti Gr-1 antibody was used to detect the function of the anti-Gr1 treatment in breast cancer.Results: The operative stress impaired the overall survival, leading to an increased number of MDSCs that preferentially infiltrated the tumor microenvironment and promoted tumor metastasis. In both in vitro and in vivo assays, MDSCs induced the epithelial-mesenchymal transition (EMT) of tumor cells through the up-regulation of TGF-beta1, VEGF, and IL-10. Furthermore, a treatment strategy of MDSC depletion was found to reduce pulmonary metastases after operations.Conclusions: The stress of operation could impair the overall survival in mice. The infiltrated MDSCs appear to induce EMT of tumor cells and increase metastases through the up-regulation of TGF-beta1, VEGF, and IL-10 levels. MDSC depletion could be a promising treatment strategy to prevent immune evasion after operations.https://www.frontiersin.org/article/10.3389/fonc.2019.00855/fullMDSC (myeloid-derived suppressor cells)operationstressbreast cancermetastasis
spellingShingle Xuelei Ma
Manni Wang
Tao Yin
Yunuo Zhao
Xiawei Wei
Myeloid-Derived Suppressor Cells Promote Metastasis in Breast Cancer After the Stress of Operative Removal of the Primary Cancer
Frontiers in Oncology
MDSC (myeloid-derived suppressor cells)
operation
stress
breast cancer
metastasis
title Myeloid-Derived Suppressor Cells Promote Metastasis in Breast Cancer After the Stress of Operative Removal of the Primary Cancer
title_full Myeloid-Derived Suppressor Cells Promote Metastasis in Breast Cancer After the Stress of Operative Removal of the Primary Cancer
title_fullStr Myeloid-Derived Suppressor Cells Promote Metastasis in Breast Cancer After the Stress of Operative Removal of the Primary Cancer
title_full_unstemmed Myeloid-Derived Suppressor Cells Promote Metastasis in Breast Cancer After the Stress of Operative Removal of the Primary Cancer
title_short Myeloid-Derived Suppressor Cells Promote Metastasis in Breast Cancer After the Stress of Operative Removal of the Primary Cancer
title_sort myeloid derived suppressor cells promote metastasis in breast cancer after the stress of operative removal of the primary cancer
topic MDSC (myeloid-derived suppressor cells)
operation
stress
breast cancer
metastasis
url https://www.frontiersin.org/article/10.3389/fonc.2019.00855/full
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AT taoyin myeloidderivedsuppressorcellspromotemetastasisinbreastcancerafterthestressofoperativeremovaloftheprimarycancer
AT yunuozhao myeloidderivedsuppressorcellspromotemetastasisinbreastcancerafterthestressofoperativeremovaloftheprimarycancer
AT xiaweiwei myeloidderivedsuppressorcellspromotemetastasisinbreastcancerafterthestressofoperativeremovaloftheprimarycancer