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Updated: Aug 6, 2025
Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
Macrophages M2 polarization is involved in lapatinib-mediated chemopreventive effects in the lung cancer
Muhammad Tariq1, Nadia Hussain2, Kanwal Rehman3
1Department of Pharmacology, Lahore Pharmacy College Lahore, Pakistan; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Abstract:
M2 polarized tumor-associated macrophages (TAMs) have a multifunctional role in cancer initiation, progression, metastasis, and contribute to chemotherapeutic resistance. Therefore, identifying M2 polarized TAMs is a potential target for cancer therapeutic intervention. The underlying mechanism that target the TAMs M2 polarized macrophages remains primarily uncharacterized; however, only a few compounds have been identified that inhibit TAMs M2 polarized macrophages. In this research, we investigated that lapatinib could effectively suppress the expression of IL_13-induced M2 polarized macrophages surface markers i.e., CD163 and CD206, and downregulation of M2 genes such as Fizz1, Mrc1, Arg1, IL-10, Ym1, nd CCL2 in vitro. Moreover, lapatinib abrogated the M2 polarized macrophage-mediated cancer cells invasion and migration. Mechanistically, in our study, lapatinib inhibited IL-13 triggered STAT6 phosphorylation. Furthermore, in LLCs tumor model, lapatinib significantly reduced tumorigenesis, followed by the downregulation of percentages of M2 marker CD206+ and CD68+ in the tumor. This downregulation correlates with chemopreventive effect of lapatinib. All taken together, these results demonstrated that lapatinib effectively prevents the macrophage M2 polarization and indicates a potential mechanism for preventing the tumor growth via M2 polarized polarization intervention.
Insights
Lapatinib effectively suppresses M2 polarized macrophages, key drivers of tumor growth and drug resistance. This study reveals lapatinib
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- M2 polarized tumor-associated macrophages (TAMs) promote cancer progression and chemoresistance.
- Targeting M2 TAMs is a promising therapeutic strategy, but mechanisms remain unclear.
- Few compounds effectively inhibit M2 TAMs.
Purpose of the Study:
- To investigate lapatinib's effect on M2 TAMs.
- To elucidate the mechanism by which lapatinib targets M2 TAMs.
- To evaluate lapatinib's therapeutic potential in a cancer model.
Main Methods:
- In vitro assessment of lapatinib on IL-13-induced M2 polarization markers (CD163, CD206) and genes (Fizz1, Mrc1, Arg1, IL-10, Ym1, CCL2).
- Evaluation of lapatinib's impact on M2 TAM-mediated cancer cell invasion and migration.
- In vivo study using a LLCs tumor model to assess lapatinib's effect on tumorigenesis and M2 marker expression (CD206, CD68).
- Analysis of STAT6 phosphorylation pathway inhibition by lapatinib.
Main Results:
- Lapatinib suppressed IL-13-induced M2 macrophage markers and M2 gene expression in vitro.
- Lapatinib inhibited M2 TAM-driven cancer cell invasion and migration.
- Lapatinib treatment reduced tumor growth in LLCs model, correlating with decreased CD206+ and CD68+ M2 markers.
- Lapatinib inhibited IL-13-induced STAT6 phosphorylation.
Conclusions:
- Lapatinib effectively prevents M2 macrophage polarization.
- Lapatinib's mechanism involves inhibiting the IL-13/STAT6 pathway.
- Lapatinib demonstrates chemopreventive effects and potential for tumor growth inhibition via M2 TAM targeting.
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