DMF Activates NRF2 to Inhibit the Pro-Invasion Ability of TAMs in Breast Cancer
Tumor-associated macrophages (TAMs) account for more than 50% of the cells in the tumor immune microenvironment of patients with breast cancer. A high TAM density is associated with a poor clinical prognosis. Targeting TAMs is a promising therapeutic strategy because they promote tumor growth, devel...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.706448/full |
| _version_ | 1819136575934562304 |
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| author | Ying Li Ying Li Yaxu Jia Yurong Xu Kan Li |
| author_facet | Ying Li Ying Li Yaxu Jia Yurong Xu Kan Li |
| author_sort | Ying Li |
| collection | DOAJ |
| description | Tumor-associated macrophages (TAMs) account for more than 50% of the cells in the tumor immune microenvironment of patients with breast cancer. A high TAM density is associated with a poor clinical prognosis. Targeting TAMs is a promising therapeutic strategy because they promote tumor growth, development, and metastasis. In this study, we found that dimethyl formamide (DMF) significantly inhibited the tumor invasion-promoting ability of TAMs in the co-culture system and further showed that DMF functioned by reducing reactive oxygen species (ROS) production in TAMs. The orthotopic 4T1 cell inoculation model and the spontaneous mouse mammary tumor virus-polyoma middle tumor-antigen tumor model were used to evaluate the antitumor effect of DMF. The results showed that DMF significantly inhibited tumor metastasis and increased T-cell infiltration into the tumor microenvironment. Mechanistically, NRF2 activation was necessary for DMF to exert its function, and DMF can play a role in breast cancer as an anticancer drug targeting TAMs. |
| first_indexed | 2024-12-22T10:37:10Z |
| format | Article |
| id | doaj.art-96663417dd684386b5495894100e75a6 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-22T10:37:10Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-96663417dd684386b5495894100e75a62022-12-21T18:29:08ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-08-011110.3389/fonc.2021.706448706448DMF Activates NRF2 to Inhibit the Pro-Invasion Ability of TAMs in Breast CancerYing Li0Ying Li1Yaxu Jia2Yurong Xu3Kan Li4Department of Clinical Laboratory, Affiliated Zhongda Hospital of Southeast University, Nanjing, ChinaDepartment of Epidemiology, School of Public Health of Suzhou University, Suzhou, ChinaDepartment of Clinical Laboratory, Affiliated Zhongda Hospital of Southeast University, Nanjing, ChinaDepartment of Clinical Laboratory, Affiliated Zhongda Hospital of Southeast University, Nanjing, ChinaDepartment of Clinical Laboratory, Affiliated Zhongda Hospital of Southeast University, Nanjing, ChinaTumor-associated macrophages (TAMs) account for more than 50% of the cells in the tumor immune microenvironment of patients with breast cancer. A high TAM density is associated with a poor clinical prognosis. Targeting TAMs is a promising therapeutic strategy because they promote tumor growth, development, and metastasis. In this study, we found that dimethyl formamide (DMF) significantly inhibited the tumor invasion-promoting ability of TAMs in the co-culture system and further showed that DMF functioned by reducing reactive oxygen species (ROS) production in TAMs. The orthotopic 4T1 cell inoculation model and the spontaneous mouse mammary tumor virus-polyoma middle tumor-antigen tumor model were used to evaluate the antitumor effect of DMF. The results showed that DMF significantly inhibited tumor metastasis and increased T-cell infiltration into the tumor microenvironment. Mechanistically, NRF2 activation was necessary for DMF to exert its function, and DMF can play a role in breast cancer as an anticancer drug targeting TAMs.https://www.frontiersin.org/articles/10.3389/fonc.2021.706448/fullTAMsDMFNRF2anti-cancer drugbreast cancer |
| spellingShingle | Ying Li Ying Li Yaxu Jia Yurong Xu Kan Li DMF Activates NRF2 to Inhibit the Pro-Invasion Ability of TAMs in Breast Cancer Frontiers in Oncology TAMs DMF NRF2 anti-cancer drug breast cancer |
| title | DMF Activates NRF2 to Inhibit the Pro-Invasion Ability of TAMs in Breast Cancer |
| title_full | DMF Activates NRF2 to Inhibit the Pro-Invasion Ability of TAMs in Breast Cancer |
| title_fullStr | DMF Activates NRF2 to Inhibit the Pro-Invasion Ability of TAMs in Breast Cancer |
| title_full_unstemmed | DMF Activates NRF2 to Inhibit the Pro-Invasion Ability of TAMs in Breast Cancer |
| title_short | DMF Activates NRF2 to Inhibit the Pro-Invasion Ability of TAMs in Breast Cancer |
| title_sort | dmf activates nrf2 to inhibit the pro invasion ability of tams in breast cancer |
| topic | TAMs DMF NRF2 anti-cancer drug breast cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.706448/full |
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