Tumorigenicity of EGFR- and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages
Basal-like breast cancer (BLBC) has a clinically aggressive nature. It is prevalent in young women and is known to often relapse rapidly. To date, the molecular mechanisms regarding the aggressiveness of BLBC have not been fully understood. In the present study, mechanisms of aggressiveness of BLBC...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/1443 |
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| author | Daeun You Hyungjoo Kim Yisun Jeong Sun Young Yoon Eunji Lo Sangmin Kim Jeong Eon Lee |
| author_facet | Daeun You Hyungjoo Kim Yisun Jeong Sun Young Yoon Eunji Lo Sangmin Kim Jeong Eon Lee |
| author_sort | Daeun You |
| collection | DOAJ |
| description | Basal-like breast cancer (BLBC) has a clinically aggressive nature. It is prevalent in young women and is known to often relapse rapidly. To date, the molecular mechanisms regarding the aggressiveness of BLBC have not been fully understood. In the present study, mechanisms of aggressiveness of BLBC involving EGFR and/or HER2 expression and interactions between tumor and tumor-associated macrophages (TAMs) were explored. The prognosis of breast cancer patients who underwent surgery at Samsung Medical Center was analyzed. It was found that the co-expression of EGFR and HER2 was associated with a worse prognosis. Therefore, we generated EGFR-positive BLBC cells with stable HER2 overexpression and analyzed the profile of secretory cytokines. Chemokine (C-C motif) ligand 2 (CCL2) expression was increased in HER2-overexpressed BLBC cells. Recombinant human CCL2 treatment augmented the motility of TAMs. In addition, the conditioned culture media of HER2-overexpressed BLBC cells increased the motility of TAMs. Furthermore, activation of TAMs by CCL2 or the conditioned culture media of HER2-overexpressed cells resulted in the production of pro-inflammatory cytokines, such as IL-8 and IL-1β. These observations reveal that CCL2 derived from EGFR and HER2 co-expressed BLBC cells can lead to increased TAM recruitment and the induction of IL-8 and IL-1β from recruited TAMs, triggering the tumorigenesis of breast cancer with the expression of both EGFR and HER2. Our findings demonstrate that EGFR+ and HER2+ BLBC aggressiveness is partially mediated through the interaction between BLBC and TAMs recruited by CCL2. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:21:03Z |
| publishDate | 2023-01-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a975c0ae91644b269c70cda0f8e69e2b2023-11-30T22:40:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242144310.3390/ijms24021443Tumorigenicity of EGFR- and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated MacrophagesDaeun You0Hyungjoo Kim1Yisun Jeong2Sun Young Yoon3Eunji Lo4Sangmin Kim5Jeong Eon Lee6Department of Breast Cancer Center, Samsung Medical Center, Seoul 06351, Republic of KoreaDepartment of Breast Cancer Center, Samsung Medical Center, Seoul 06351, Republic of KoreaDepartment of Breast Cancer Center, Samsung Medical Center, Seoul 06351, Republic of KoreaDepartment of Breast Cancer Center, Samsung Medical Center, Seoul 06351, Republic of KoreaDepartment of Breast Cancer Center, Samsung Medical Center, Seoul 06351, Republic of KoreaDepartment of Breast Cancer Center, Samsung Medical Center, Seoul 06351, Republic of KoreaDepartment of Breast Cancer Center, Samsung Medical Center, Seoul 06351, Republic of KoreaBasal-like breast cancer (BLBC) has a clinically aggressive nature. It is prevalent in young women and is known to often relapse rapidly. To date, the molecular mechanisms regarding the aggressiveness of BLBC have not been fully understood. In the present study, mechanisms of aggressiveness of BLBC involving EGFR and/or HER2 expression and interactions between tumor and tumor-associated macrophages (TAMs) were explored. The prognosis of breast cancer patients who underwent surgery at Samsung Medical Center was analyzed. It was found that the co-expression of EGFR and HER2 was associated with a worse prognosis. Therefore, we generated EGFR-positive BLBC cells with stable HER2 overexpression and analyzed the profile of secretory cytokines. Chemokine (C-C motif) ligand 2 (CCL2) expression was increased in HER2-overexpressed BLBC cells. Recombinant human CCL2 treatment augmented the motility of TAMs. In addition, the conditioned culture media of HER2-overexpressed BLBC cells increased the motility of TAMs. Furthermore, activation of TAMs by CCL2 or the conditioned culture media of HER2-overexpressed cells resulted in the production of pro-inflammatory cytokines, such as IL-8 and IL-1β. These observations reveal that CCL2 derived from EGFR and HER2 co-expressed BLBC cells can lead to increased TAM recruitment and the induction of IL-8 and IL-1β from recruited TAMs, triggering the tumorigenesis of breast cancer with the expression of both EGFR and HER2. Our findings demonstrate that EGFR+ and HER2+ BLBC aggressiveness is partially mediated through the interaction between BLBC and TAMs recruited by CCL2.https://www.mdpi.com/1422-0067/24/2/1443EGFRHER2basal-like breast cancerCCL2tumor-associated macrophage |
| spellingShingle | Daeun You Hyungjoo Kim Yisun Jeong Sun Young Yoon Eunji Lo Sangmin Kim Jeong Eon Lee Tumorigenicity of EGFR- and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages International Journal of Molecular Sciences EGFR HER2 basal-like breast cancer CCL2 tumor-associated macrophage |
| title | Tumorigenicity of EGFR- and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages |
| title_full | Tumorigenicity of EGFR- and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages |
| title_fullStr | Tumorigenicity of EGFR- and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages |
| title_full_unstemmed | Tumorigenicity of EGFR- and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages |
| title_short | Tumorigenicity of EGFR- and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages |
| title_sort | tumorigenicity of egfr and or her2 positive breast cancers is mediated by recruitment of tumor associated macrophages |
| topic | EGFR HER2 basal-like breast cancer CCL2 tumor-associated macrophage |
| url | https://www.mdpi.com/1422-0067/24/2/1443 |
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