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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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Autores principales: You, Daeun, Kim, Hyungjoo, Jeong, Yisun, Yoon, Sun Young, Lo, Eunji, Kim, Sangmin, Lee, Jeong Eon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866454/
https://www.ncbi.nlm.nih.gov/pubmed/36674955
http://dx.doi.org/10.3390/ijms24021443
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author You, Daeun
Kim, Hyungjoo
Jeong, Yisun
Yoon, Sun Young
Lo, Eunji
Kim, Sangmin
Lee, Jeong Eon
author_facet You, Daeun
Kim, Hyungjoo
Jeong, Yisun
Yoon, Sun Young
Lo, Eunji
Kim, Sangmin
Lee, Jeong Eon
author_sort You, Daeun
collection PubMed
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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spelling pubmed-98664542023-01-22 Tumorigenicity of EGFR- and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages You, Daeun Kim, Hyungjoo Jeong, Yisun Yoon, Sun Young Lo, Eunji Kim, Sangmin Lee, Jeong Eon Int J Mol Sci Article 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. MDPI 2023-01-11 /pmc/articles/PMC9866454/ /pubmed/36674955 http://dx.doi.org/10.3390/ijms24021443 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
You, Daeun
Kim, Hyungjoo
Jeong, Yisun
Yoon, Sun Young
Lo, Eunji
Kim, Sangmin
Lee, Jeong Eon
Tumorigenicity of EGFR- and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866454/
https://www.ncbi.nlm.nih.gov/pubmed/36674955
http://dx.doi.org/10.3390/ijms24021443
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