BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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Regulation of tumor-associated macrophage (TAM) differentiation by NDRG2 expression in breast cancer cells

  • Lee, Soyeon (Department of Biological Science and the Cellular Heterogeneity Research Center, Sookmyung Women's University) ;
  • Lee, Aram (Department of Biological Science and the Cellular Heterogeneity Research Center, Sookmyung Women's University) ;
  • Lim, Jihyun (Department of Biological Science and the Cellular Heterogeneity Research Center, Sookmyung Women's University) ;
  • Lim, Jong-Seok (Department of Biological Science and the Cellular Heterogeneity Research Center, Sookmyung Women's University)
  • 투고 : 2021.08.13
  • 심사 : 2021.10.26
  • 발행 : 2022.02.28
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초록

Macrophages are a major cellular component of innate immunity and are mainly known to have phagocytic activity. In the tumor microenvironment (TME), they can be differentiated into tumor-associated macrophages (TAMs). As the most abundant immune cells in the TME, TAMs promote tumor progression by enhancing angiogenesis, suppressing T cells and increasing immunosuppressive cytokine production. N-myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor gene, whose expression is down-regulated in various cancers. However, the effect of NDRG2 on the differentiation of macrophages into TAMs in breast cancer remains elusive. In this study, we investigated the effect of NDRG2 expression in breast cancer cells on the differentiation of macrophages into TAMs. Compared to tumor cell-conditioned medium (TCCM) from 4T1-mock cells, TCCM from NDRG2-over-expressing 4T1 mouse breast cancer cells did not significantly change the morphology of RAW 264.7 cells. However, TCCM from 4T1-NDRG2 cells reduced the mRNA levels of TAM-related genes, including MR1, IL-10, ARG1 and iNOS, in RAW 264.7 cells. In addition, TCCM from 4T1-NDRG2 cells reduced the expression of TAM-related surface markers, such as CD206, in peritoneal macrophages (PEM). The mRNA expression of TAM-related genes, including IL-10, YM1, FIZZ1, MR1, ARG1 and iNOS, was also downregulated by TCCM from 4T1-NDRG2 cells. Remarkably, TCCM from 4T1-NDRG2 cells reduced the expression of PD-L1 and Fra-1 as well as the production of GM-CSF, IL-10 and ROS, leading to the attenuation of T cell-inhibitory activity of PEM. These data showed that compared with TCCM from 4T1-mock cells, TCCM from 4T1-NDRG2 cells suppressed the TAM differentiation and activation. Collectively, these results suggest that NDRG2 expression in breast cancer may reduce the differentiation of macrophages into TAMs in the TME.

키워드

과제정보

This study was supported by grants from the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT, Republic of Korea (NRF-2016R1A5A1011974 and 2019R1A2C1088825). J.L. was supported by a grant from the National Research Foundation of Korea (NRF-2019R1I1A1A01058629).

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