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Updated: Oct 4, 2025
Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion
Published on: April 2, 2020
CXCR4 Knockdown Via CRISPR/CAS9 in a Tumor-Associated Macrophage Model Decreases Human Breast Cancer Cell Migration
Luis Jaramillo-Valverde1,2, Kelly S Levano1, Silvia Capristano1
1Biotechnology and Molecular Biology Laboratory, Instituto Nacional de Salud, Lima, PER.
Abstract:
Introduction Breast cancer is the leading cause of cancer-related deaths in women worldwide with the majority of deaths due to metastasis. The development of metastasis is closely related to the tumor microenvironment where tumor-associated macrophages (TAMs) are the main immune cell component playing a crucial role in tumor migration. Key players in tumor progression, metastasis and survival are the receptor CXCR4 and its ligand CXCL12. CXCR4 is expressed in multiple cell types including macrophages and breast cancer cells. Many studies have focus on the role of CXCR4 expressed in breast cancer cells. Methods In this study, we investigated the role of CXCR4 expressed in TAMs on breast cancer cell migration by reducing CXCR4 expression via CRISPR-CAS9 system in differentiated THP-1 cells (a TAMs model). Results According to wound healing migration assay, MCF7 cancer cells co-cultured with genetically edited dTHP-1 cells have a lower migration rate as compared to MCF7 cancer cells co-cultured with unedited and dTHP-1 cells. Conclusion The study demonstrates the role of CXCR4 on breast cancer cell migration through TAM-cancer cell crosstalk.
Insights
Tumor-associated macrophages (TAMs) influence breast cancer metastasis. Targeting the CXCR4 receptor on TAMs can reduce breast cancer cell migration, offering new therapeutic strategies.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Breast cancer metastasis is a leading cause of death, driven by the tumor microenvironment.
- Tumor-associated macrophages (TAMs) are key immune cells in this microenvironment, influencing tumor cell migration.
- The CXCR4 receptor and its ligand CXCL12 are critical for tumor progression and survival, with CXCR4 expressed on both TAMs and cancer cells.
Purpose of the Study:
- To investigate the role of CXCR4 expressed specifically on TAMs in breast cancer cell migration.
- To understand the crosstalk between TAMs and breast cancer cells mediated by CXCR4.
Main Methods:
- Differentiated THP-1 cells were used as a model for TAMs.
- CRISPR-Cas9 gene editing was employed to reduce CXCR4 expression in these TAM models.
- MCF7 breast cancer cells were co-cultured with genetically edited and unedited TAM models.
- Wound healing migration assays were performed to assess cancer cell migration rates.
Main Results:
- Co-culture with CXCR4-edited TAMs significantly reduced the migration rate of MCF7 breast cancer cells compared to controls.
- This indicates that CXCR4 on TAMs plays a crucial role in promoting breast cancer cell migration.
Conclusions:
- The study highlights the significant role of CXCR4 expressed on TAMs in facilitating breast cancer cell migration.
- Targeting the TAM-CXCR4 axis represents a potential therapeutic strategy to inhibit breast cancer metastasis.
