Cover image of the article: Investigating the Role of Tumor-Associated Macrophages in the Resistance of Brain Metastatic Tumor Cells to Paclitaxel in Two- Dimensional and Three-Dimensional Cell Culture Conditions

Image Credit:Koomesh

Investigating the Role of Tumor-Associated Macrophages in the Resistance of Brain Metastatic Tumor Cells to Paclitaxel in Two- Dimensional and Three-Dimensional Cell Culture Conditions

Authors

Mahnaz Siahi1, Mohammad Kamalabadi FarahaniMohammad Kamalabadi Farahani ORCID2,*, Amir AtashiAmir Atashi ORCID3, Sepehr ZamaniSepehr Zamani ORCID4
1Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
2Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
3Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Shahroud University of Medical Sciences, Shahroud, Iran
4Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
*Corresponding Author: Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran. Email: kamalabadi@shmu.ac.ir

Koomesh:Vol. 27, issue 4; e149732
Published online:Aug 18, 2025
Article type:Research Article
How to Cite:Siahi M, Kamalabadi Farahani M, Atashi A, Zamani S. Investigating the Role of Tumor-Associated Macrophages in the Resistance of Brain Metastatic Tumor Cells to Paclitaxel in Two- Dimensional and Three-Dimensional Cell Culture Conditions. Koomesh. 2025;27(4):e149732. doi: https://doi.org/10.69107/koomesh-149732

Abstract

Background: Brain metastasis is a devastating complication in breast cancer patients. Tumor-associated macrophages (TAMs) are cells in innate immunity, repair, and homeostasis. These cells play an important role in drug resistance in the metastatic microenvironment.

Objectives: In this study, the roles of TAMs in the resistance of brain metastatic cells to paclitaxel were evaluated in two-dimensional and three-dimensional cell culture conditions

Methods: After the generation of a mouse model of breast cancer, brain metastatic tumor cells named 4T1B were isolated from brain metastasis lesions in mice. Simultaneous cultivation of RAW macrophage cells and 4T1B tumor cells was done in 2D and 3D (multicellular spheroids) culture mediums. The cytotoxic activity of paclitaxel on cells was evaluated by MTT assay.

Results: The results of this study show that TAMs cause a significant increase in paclitaxel resistance in brain metastatic cells only in 3D cell culture. Also, spheroidal formation was greater in terms of number and size when metastatic cells and macrophages were cultured simultaneously.

Conclusion: Therefore, according to the results of this study, it can be concluded that tumor-related macrophages increased brain metastatic cells in terms of spheroid formation, which indicates that they are cultured in three-dimensional conditions. Also, these cells reduce the response to treatment, or, in other words, drug resistance. These results may provide useful insights for future studies in cancer chemoresistance.

 

 

Highlights

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Copyright

© 2025, Author(s). This open-access article is available under the Creative Commons Attribution 4.0 (CC BY 4.0) International License (https://creativecommons.org/licenses/by/4.0/), which allows for unrestricted use, distribution, and reproduction in any medium, provided that the original work is properly cited.

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Mahnaz SiahiPubMedScholar
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