Epithelial-mesenchymal transition and tumor-associated macrophage axis in metastatic breast cancer: converging mechanisms and therapeutic perspectives.

Breast cancer is a leading cause of cancer-related death in women worldwide, mainly attributable to metastatic progression accounting for about 90 % of these fatalities. The metastatic cascade can be initiated by epithelial-mesenchymal transition (EMT), a molecular and cellular program in which cancer cells lose their cell-cell junctions and acquire a more invasive phenotype. EMT is induced by a range of signaling molecules and growth factors, contributing significantly to the metastatic capability of cancer cells. Within the tumor microenvironment, tumor-associated macrophages (TAMs) can promote EMT through secretion of such molecules including chemokines, Wnt, IL-6, and TGF-β. Additionally, tumor cells secrete chemokines that drive the differentiation of macrophages toward an anti-inflammatory, pro-tumorigenic phenotype. This alliance between breast cancer cells and TAMs increases tumorigenicity and facilitates metastasis, highlighting a critical field of study for the development of novel and more efficient treatments in breast cancer. In this review, we discuss the mechanisms of TAM and EMT interaction in breast cancer progression and metastasis, and potential therapeutic approaches to target this crosstalk.