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Tumor-associated macrophages of the M1/M2 phenotype are involved in the regulation of malignant biological behavior of breast cancer cells through the EMT pathway

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Abstract

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. More and more studies have shown that the tumor immune microenvironment (TME) of TNBC is closely related to its poor prognosis and early metastasis. We try to explain how tumor-associate macrophages (TAMs), an important component of the TME, function in the matrix of TNBC. Therefore, we induced THP-1 cells to become M1-TAMs and M2-TAMs, investigated their influence on breast cancer cells. 82 TNBC paraffin samples were made into tissue microarrays. The expression of macrophages makers were measured by immunohistochemistry. Scratch assay, Transwell assay, CCK-8 cell proliferation assay were performed in the co-culture system of breast cancer cells lines and macrophages to observe the invasion and proliferation ability of breast cancer cell lines. Western Blot (WB) was performed to detect the expression of E-cadherin (CDH1) and N-cadherin (CDH2). M2-TAMs were more numerous than M1-TAMs in the matrix of TNBC cancer nests and associated with poor prognosis. M2-TAMs promoted the invasion, migration, and proliferation of TNBC cells. M1-TAMs had inhibitory effects. In MCF-7 cells, WB showed a decrease in CDH1 and an increase in CDH2. In MDA-MB-231 cells and BT549 cells, CDH2 expression was reduced and CDH1 expression was increased. All of the above results were statistically significant, p < 0.001. M2-TAMs were more numerous in TNBC and associated with poor prognosis. M2-TAMs promoted the invasion, migration, and proliferation of breast cancer cells. The mechanism may be related to the epithelial-mesenchymal transition.

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Acknowledgements

Thanks to all the peer reviewers and editors for their opinions and suggestions.

Funding

The present study was supported by the Innovative Research Group Project of the National Natural Science Foundation of China (No. 81872055).

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Authors and Affiliations

  1. Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China

    Zhuo Chen

  2. Division of Life Sciences and Medicine, Department of Pathology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China

    Jing Wu & Jie He

  3. Division of Life Sciences and Medicine, Academic Planning and Management Office, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China

    Liang Wang

  4. Laboratory Department, Anhui Province Hospital of Integrated Traditional Chinese and Western Medicine, Hefei, Anhui, People’s Republic of China

    Hua Zhao

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  1. Zhuo Chen
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Chen, Z., Wu, J., Wang, L. et al. Tumor-associated macrophages of the M1/M2 phenotype are involved in the regulation of malignant biological behavior of breast cancer cells through the EMT pathway. Med Oncol 39, 83 (2022). https://doi.org/10.1007/s12032-022-01670-7

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