Bisphenol A triggers adipocyte dysfunction, thereby fostering triple-negative breast cancer aggressiveness

Bisphenol A (BPA) is an organic compound widely used in the production of polycarbonate plastics and epoxy resins. As a pervasive environmental pollutant, BPA accumulates in adipose tissue (AT) due to its lipophilic properties. AT, an endocrine organ central to homeostasis, constitutes the main component of breast stroma and plays a pivotal role in the microenvironment of breast cancer, including triple-negative breast cancer (TNBC). This study investigated how BPA disrupts adipocyte differentiation and metabolism, and the subsequent effects on the crosstalk between adipocytes and TNBC cells. We induced adipogenic differentiation of preadipocytes in the presence of BPA and evaluated alterations in differentiation and cytokine secretion. TNBC cells were cultured in homotypic and heterotypic organoids, exposing them to BPA either directly or indirectly, through a conditioned medium of BPA-treated adipocytes. BPA exposure altered adipocyte differentiation, reducing lipid accumulation and perturbing cytokines release, leading to the upregulation of molecules involved in cell migration and invasiveness. TNBC cells exposed to conditioned medium of BPA-treated adipocytes exhibited enhanced growth, migration and invasiveness, whereas direct BPA treatment did not induce significant changes. These indirect effects were, at least in part, mediated by SDF1α and GAS1. Moreover, TNBC organoids showed increased infiltrative capacity when co-cultured with BPA-conditioned adipocytes. These findings highlight the profound impact of environmental pollution on cancer progression. BPA perturbates adipose differentiation, creating a dysfunctional adipocyte that fosters cancer growth and invasiveness in TNBC. This study underscores the impact of environmental pollutants on tumour progression by revealing the importance of BPA perturbation on tissue homeostasis and how this could promote cancer.