Unveiling the contribution of tumor-associated macrophages in driving epithelial-mesenchymal transition: a review of mechanisms and therapeutic Strategies

Front Pharmacol. 2024 Sep 2:15:1404687. doi: 10.3389/fphar.2024.1404687. eCollection 2024.

Abstract

Tumor-associated macrophages (TAMs), fundamental constituents of the tumor microenvironment (TME), significantly influence cancer development, primarily by promoting epithelial-mesenchymal transition (EMT). EMT endows cancer cells with increased motility, invasiveness, and resistance to therapies, marking a pivotal juncture in cancer progression. The review begins with a detailed exposition on the origins of TAMs and their functional heterogeneity, providing a foundational understanding of TAM characteristics. Next, it delves into the specific molecular mechanisms through which TAMs induce EMT, including cytokines, chemokines and stromal cross-talking. Following this, the review explores TAM-induced EMT features in select cancer types with notable EMT characteristics, highlighting recent insights and the impact of TAMs on cancer progression. Finally, the review concludes with a discussion of potential therapeutic targets and strategies aimed at mitigating TAM infiltration and disrupting the EMT signaling network, thereby underscoring the potential of emerging treatments to combat TAM-mediated EMT in cancer. This comprehensive analysis reaffirms the necessity for continued exploration into TAMs' regulatory roles within cancer biology to refine therapeutic approaches and improve patient outcomes.

Keywords: CSF1R, colony-stimulating factor 1 receptor; ECM, extracellular matrix; EMT, epithelialmesenchymal transition; TAM, tumor associated macrophage; TME, tumor microenvironment.

Publication types

  • Review

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research was supported by the Natural Science Foundation of Liaoning Province of China (Grant No. 2020-MS-187). The Foundation provided generous financial support for the research activities. Specifically, they supported the experimental design and data collection phases of the study. We gratefully acknowledge the Natural Science Foundation of Liaoning Province of China (2020-MS-187) for the generous financial support. Additionally, this work was supported by the Zhejiang Provincial Natural Science Foundation of China under Grant Nos. LHDMY22H310001, LGD22H160002, LBY23H200004, LTGD24H160006, LTGD23H160001, LTGY23H010007, LBY23H200004, and LTGD24H160006.