4T1 breast cancer cells exposed to extracellular vesicles from MDA-MB-231 cells stimulated with Bisphenol A increase the growth of mammary tumors and metastasis in female Balb/cJ mice.

Breast cancer is the most prevalent neoplasia in women worldwide. Triple negative breast cancer (TNBC) is a subtype characterized by the absence of estrogen receptor, progesterone receptor and HER2 expression. Bisphenol A (BPA) is a chemical used in the synthesis of polycarbonate plastics and epoxy resins and its intake is related with breast cancer progression. Extracellular vesicles (EVs) are vesicles released by cells that mediate intercellular communication. However, the role of BPA in the release of EVs mediating cancer progression in TNBC remains to be studied. We hypothesize that EVs from BPA-stimulated TNBC cells promote metastasis-related processes, tumor growth and enhanced metastasis in a breast cancer mouse model. This study aims to evaluate the functional role of EVs from BPA-stimulated TNBC cells in metastasis-related processes and breast cancer progression using "in vitro" 4T1 cells models and an "in vivo" breast cancer mouse model. Findings demonstrate that exposition of TNBC 4T1 cells to EVs from TNBC MDA-MB-231 cells stimulated with 1 μM BPA for 24 h (BPA-EVs) significantly increases migration, invasion and MMP-9 secretion, compared to 4T1 cells exposed to EVs from non-stimulated MDA-MB-231 cells (Ctrl-EVs). Furthermore, Balb/cJ mice inoculated in mammary fat pad with 4T1 cells exposed to BPA-EVs show mammary tumors with more weight and volume, and more metastatic nodules in lung and liver than Balb/cJ mice inoculated with 4T1 cells exposed to Ctrl-EVs. In conclusion, BPA-EVs represent a significant mediator of TNBC progression, which defining the EVs as a novel element through which BPA promotes breast cancer progression.