Tumorigenicity of EGFR- and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages
Abstract
:1. Introduction
2. Results
2.1. Co-Expression of EGFR and HER2 Correlates with Poor Survival in Breast Cancer Patients
2.2. Co-Expression of EGFR and HER2 Promotes Invasion and Proliferation
2.3. Cytokine Secretion Profile Is Altered by HER2 Overexpression
2.4. CCL2 Expression Is Downregulated by Neratinib, a Pan-HER Inhibitor
2.5. CCL2 Mediates Motility of TAMs
3. Discussion
4. Materials and Methods
4.1. Clinicopathological Characteristics of Breast Cancer Patients
4.2. Cell Culture
4.3. HER2 Knockdown Using siRNAs
4.4. Establishment of M2-Polarized THP-1 Macrophages
4.5. Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR)
4.6. Western Blotting
4.7. Cell Invasion/Migration Assays
4.8. Cell Cycle Analysis
4.9. Human Cytokine Array
4.10. Enzyme-Linked Immunosorbent Assay (ELISA)
4.11. Immunofluorescence Staining
4.12. Immunohistochemistry (IHC)
4.13. Xenograft Studies
4.14. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variables | No. of Patients (%) |
---|---|
Age (years) | |
<50 | 597 (62.8%) |
≥50 | 363 (37.2%) |
Menopause | |
Pre. | 588 (61.9%) |
Post. | 362 (38.1%) |
ER | |
Negative (−) | 313 (35.9%) |
Positive (+) | 558 (64.1%) |
PR | |
Negative (−) | 468 (53.1%) |
Positive (+) | 413 (46.9%) |
EGFR | |
Negative (−) | 819 (86.3%) |
Positive (+) | 130 (13.7%) |
HER2 | |
Negative (−) | 715 (75.3%) |
Positive (+) | 235 (24.7%) |
TP53 | |
Negative (−) | 328 (41.8%) |
Positive (+) | 457 (58.2%) |
Operation | |
BCS 1 | 359 (37.8%) |
MRM 2 | 591 (62.2%) |
T stage | |
T1 | 391 (41.2%) |
T2 | 494 (52.0%) |
T3 | 62 (6.5%) |
T4 | 3 (0.3%) |
n stage | |
N0 | 498 (52.4%) |
N1 | 248 (26.1%) |
N2 | 116 (12.2%) |
N3 | 88 (9.3%) |
Stage | |
I | 258 (27.4%) |
IIA | 332 (35.2%) |
IIB | 135 (14.3%) |
IIIA | 130 (13.8%) |
IIIB | 2 (0.2%) |
IIIC | 85 (9.0%) |
Nuclear grade | |
Low | 86 (9.1%) |
Intermediate | 471 (49.6%) |
High | 355 (37.4%) |
Unknown | 38 (4.0%) |
CK 5/6 | |
Negative (−) | 819 (86.2%) |
Positive (+) | 131 (13.8%) |
Radiotherapy | |
Yes | 532 (61.6%) |
No | 332 (38.4%) |
Unknown | 15 (1.7%) |
Chemotherapy | |
Yes | 794 (85.3%) |
No | 137 (14.7%) |
Unknown | 19 (2.0%) |
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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://doi.org/10.3390/ijms24021443
You D, Kim H, Jeong Y, Yoon SY, Lo E, Kim S, Lee JE. Tumorigenicity of EGFR- and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages. International Journal of Molecular Sciences. 2023; 24(2):1443. https://doi.org/10.3390/ijms24021443
Chicago/Turabian StyleYou, Daeun, Hyungjoo Kim, Yisun Jeong, Sun Young Yoon, Eunji Lo, Sangmin Kim, and Jeong Eon Lee. 2023. "Tumorigenicity of EGFR- and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages" International Journal of Molecular Sciences 24, no. 2: 1443. https://doi.org/10.3390/ijms24021443