Tumorigenicity of EGFR-and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages

Sep 24, 2026

Uploaded by dhado

Basal-like breast cancer (BLBC) is clinically aggressive, common in young women, and often relapses rapidly, yet the molecular basis of its severity remains insufficiently defined. This study examines aggressiveness mechanisms involving EGFR and/or HER2 signaling and tumor–tumor-associated macrophage interactions. Patient prognosis data from Samsung Medical Center links EGFR and HER2 co-expression to worse outcomes. Mechanistically, HER2-overexpressing BLBC increases CCL2, which enhances TAM motility and stimulates production of IL-8 and IL-1β, promoting tumorigenesis.

LanguageEnglish

CategoryHealthcare

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Pages15

Reading Time38 min

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Abstract

Introduction

Article Tumorigenicity of EGFR-and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages Daeun You 1,2,†, Hyungjoo Kim 1,3,†, Yisun Jeong 1,2, Sun Young Yoon 1,2, Eunji Lo 1,2, Sangmin Kim 1,3, * and Jeong Eon Lee 1,2,3, * Citation: You, D.; Kim, H.; Jeong, Y.; Yoon, S.Y.; Lo, E.; Kim, S.; Lee, J.E. Tumorigenicity of EGFR-and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages. Int. J. Mol. Sci. 2023, 24, 1443. [https://](https://)[ ](https://)[doi.org/10.3390/ijms24021443](doi.org/10.3390/ijms24021443) Academic Editors: Jonas Fuxe, Rainer Heuchel and Ehnman Monika Received: 15 November 2022 Revised: 27 December 2022 Accepted: 9 January 2023 Published: 11 January 2023 Copyright: © 2023 by the authors. 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://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Breast Cancer Center, Samsung Medical Center, Seoul 06351, Republic of Korea; [daeun0815@naver.com](daeun0815@naver.com) (D.Y.); [hjook1990@hanyang.ac.kr](hjook1990@hanyang.ac.kr) (H.K.); [sunrise1526@naver.com](sunrise1526@naver.com) (Y.J.); [soso66772000@naver.com](soso66772000@naver.com) (S.Y.Y.); [rej4178@naver.com](rej4178@naver.com) (E.L.) 2 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea 3 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea * Correspondence: [sangmin3005.kim@samsung.com](sangmin3005.kim@samsung.com) (S.K.); [paojlus@hanmail.net](paojlus@hanmail.net) (J.E.L.); Tel.: +82-2-2148-7312 (S.K.); +82-2-3410-3478 (J.E.L.); Fax: +82-2-3410-6982 (S.K.); +82-2-3410-0260 (J.E.L.)† These authors contributed equally to this work. Abstract: 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-1􀀌 . 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-1􀀌 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 . Keywords: EGFR; HER2; basal-like breast cancer; CCL2; tumor-associated macrophage 1. Introduction Breast cancer is the most frequent cancer in women and is known to have a complex heterogeneity at the molecular level [1] . Basal-like breast cancer (BLBC) is a subtype of breast cancer characterized by the expression of

FAQs

What does the study identify as linked to poor prognosis in breast cancer patients?

The co-expression of EGFR and HER2 is associated with a worse prognosis in patients analyzed from Samsung Medical Center.

How is CCL2 connected to tumor-associated macrophage behavior in this work?

HER2-overexpressed BLBC cells increase CCL2 expression, and recombinant human CCL2 or conditioned media enhances the motility of tumor-associated macrophages.

What downstream effects do activated tumor-associated macrophages produce?

Activation by CCL2 or conditioned media leads to production of pro-inflammatory cytokines, including IL-8 and IL-1β.

Sep 24, 2026

Uploaded by dhado