CAA-derived IL-6 induced M2 macrophage polarization by activating STAT3
Abstract Background Tumor-associated macrophages (TAMs) are the most abundant types of immune cells in the tumor microenvironment (TME) of breast cancer (BC). TAMs usually exhibit an M2 phenotype and promote tumor progression by facilitating immunosuppression. This study aimed to investigate the eff...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-10826-1 |
| _version_ | 1797832002501607424 |
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| author | Chongru Zhao Ning Zeng Xiaomei Zhou Yufang Tan Yichen Wang Jun Zhang Yiping Wu Qi Zhang |
| author_facet | Chongru Zhao Ning Zeng Xiaomei Zhou Yufang Tan Yichen Wang Jun Zhang Yiping Wu Qi Zhang |
| author_sort | Chongru Zhao |
| collection | DOAJ |
| description | Abstract Background Tumor-associated macrophages (TAMs) are the most abundant types of immune cells in the tumor microenvironment (TME) of breast cancer (BC). TAMs usually exhibit an M2 phenotype and promote tumor progression by facilitating immunosuppression. This study aimed to investigate the effect of CAA-derived IL-6 on macrophage polarization in promoting BC progression. Methods Human BC samples and adipocytes co-cultured with 4T1 BC cells were employed to explore the properties of CAAs. The co-implantation of adipocytes and 4T1 cells in mouse tumor-bearing model and tail vein pulmonary metastasis model were constructed to investigate the impact of CAAs on BC malignant progression in vivo. The functional assays, qRT-PCR, western blotting assay and ELISA assay were employed to explore the effect of CAA-derived IL-6 on macrophage polarization and programmed cell death protein ligand 1 (PD-L1) expression. Results CAAs were located at the invasive front of BC and possessed a de-differentiated fibroblast phenotype. CAAs facilitated the malignant behaviors of 4T1 cells in vitro, and promoted 4T1 tumor growth and pulmonary metastasis in vivo. The IHC staining of both human BC specimens and xenograft and the in vitro experiment indicated that CAAs could enhance infiltration of M2 macrophages in the TME of 4T1 BC. Furthermore, CAA-educated macrophages could enhance malignant behaviors of 4T1 cells in vitro. More importantly, CAAs could secret abundant IL-6 and thus induce M2 macrophage polarization by activating STAT3. In addition, CAAs could upregulate PD-L1 expression in macrophages. Conclusions Our study revealed that CAAs and CAA-educated macrophages enhanced the malignant behaviors of BC. Specifically, CAA-derived IL-6 induced migration and M2 polarization of macrophages via activation STAT3 and promoted macrophage PD-L1 expression, thereby leading to BC progression. |
| first_indexed | 2024-04-09T14:01:50Z |
| format | Article |
| id | doaj.art-12a6888b73de4d02b3af7a12fe2401d6 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-09T14:01:50Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-12a6888b73de4d02b3af7a12fe2401d62023-05-07T11:15:49ZengBMCBMC Cancer1471-24072023-05-0123111510.1186/s12885-023-10826-1CAA-derived IL-6 induced M2 macrophage polarization by activating STAT3Chongru Zhao0Ning Zeng1Xiaomei Zhou2Yufang Tan3Yichen Wang4Jun Zhang5Yiping Wu6Qi Zhang7Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Thyroid and Breast Surgery, Shenzhen Qianhai Shekou Free Trade Zone HospitalDepartment of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Tumor-associated macrophages (TAMs) are the most abundant types of immune cells in the tumor microenvironment (TME) of breast cancer (BC). TAMs usually exhibit an M2 phenotype and promote tumor progression by facilitating immunosuppression. This study aimed to investigate the effect of CAA-derived IL-6 on macrophage polarization in promoting BC progression. Methods Human BC samples and adipocytes co-cultured with 4T1 BC cells were employed to explore the properties of CAAs. The co-implantation of adipocytes and 4T1 cells in mouse tumor-bearing model and tail vein pulmonary metastasis model were constructed to investigate the impact of CAAs on BC malignant progression in vivo. The functional assays, qRT-PCR, western blotting assay and ELISA assay were employed to explore the effect of CAA-derived IL-6 on macrophage polarization and programmed cell death protein ligand 1 (PD-L1) expression. Results CAAs were located at the invasive front of BC and possessed a de-differentiated fibroblast phenotype. CAAs facilitated the malignant behaviors of 4T1 cells in vitro, and promoted 4T1 tumor growth and pulmonary metastasis in vivo. The IHC staining of both human BC specimens and xenograft and the in vitro experiment indicated that CAAs could enhance infiltration of M2 macrophages in the TME of 4T1 BC. Furthermore, CAA-educated macrophages could enhance malignant behaviors of 4T1 cells in vitro. More importantly, CAAs could secret abundant IL-6 and thus induce M2 macrophage polarization by activating STAT3. In addition, CAAs could upregulate PD-L1 expression in macrophages. Conclusions Our study revealed that CAAs and CAA-educated macrophages enhanced the malignant behaviors of BC. Specifically, CAA-derived IL-6 induced migration and M2 polarization of macrophages via activation STAT3 and promoted macrophage PD-L1 expression, thereby leading to BC progression.https://doi.org/10.1186/s12885-023-10826-1Breast cancerCancer-associated adipocytesIL-6STAT3Macrophages |
| spellingShingle | Chongru Zhao Ning Zeng Xiaomei Zhou Yufang Tan Yichen Wang Jun Zhang Yiping Wu Qi Zhang CAA-derived IL-6 induced M2 macrophage polarization by activating STAT3 BMC Cancer Breast cancer Cancer-associated adipocytes IL-6 STAT3 Macrophages |
| title | CAA-derived IL-6 induced M2 macrophage polarization by activating STAT3 |
| title_full | CAA-derived IL-6 induced M2 macrophage polarization by activating STAT3 |
| title_fullStr | CAA-derived IL-6 induced M2 macrophage polarization by activating STAT3 |
| title_full_unstemmed | CAA-derived IL-6 induced M2 macrophage polarization by activating STAT3 |
| title_short | CAA-derived IL-6 induced M2 macrophage polarization by activating STAT3 |
| title_sort | caa derived il 6 induced m2 macrophage polarization by activating stat3 |
| topic | Breast cancer Cancer-associated adipocytes IL-6 STAT3 Macrophages |
| url | https://doi.org/10.1186/s12885-023-10826-1 |
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