Extracellular Vesicles and Endocrine Disruption: How Environmental Pollutants Modulate the Loading and Release of Extracellular Vesicles for Cancer Promotion and Progression.

Intercellular communication is mediated by extracellular vesicles (EVs), particles released by all cell types that transfer bioactive cargo (proteins, lipids, nucleic acids) to recipient cells, influencing their function. Furthermore, the human population is simultaneously exposed to mixtures of endocrine-disrupting chemicals (EDCs), capable of altering hormonal homeostasis. Epidemiological and experimental evidence, in animal and cellular models, show that EDCs can contribute to the initiation, development, and progression of carcinogenesis. This review analyzes the EDC-EV-Cancer axis, connecting the biology of EVs to environmental toxicology and the processes that lead to tumor development. It has been examined how specific pollutants-arsenic, polycyclic aromatic hydrocarbons, bisphenol A, phthalates, particulate matter 2.5, and cigarette smoke-modify the secretion and content of EVs. These altered EVs may subsequently trigger critical oncogenic mechanisms in recipient cells, including proliferation, angiogenesis, migration, immunosuppression, and metastasis. Specific mechanisms, pathways, miRNAs, and proteins have been identified, following exposure to various EDCs that are capable of modulating cells and the tumor microenvironment to induce carcinogenesis and tumor progression. Therefore, EVs represent a promising platform for investigating the role of exposome in tumor development, serving as a real-time monitoring system that would allow tracking of combined and dynamic human environmental exposure and help in cancer prevention.