The Roles and Mechanisms of EVs in Disease Processes

Extracellular vesicle (EV)-mediated communication plays critical roles in the progression of many diseases, including various cancers, diabetes, Alzheimer’s disease, Parkinson’s disease, and infectious diseases. EVs mediate molecular exchange between tumor cells to decrease intratumoral heterogeneity. Cancer cell EVs may transfer pro-angiogenic factors to EVs and induce angiogenesis, contribute to immunosuppression by directly stimulating immune cells or delivering antigens to dendritic cells, and mediate premetastatic niche formation by delivering their cargo to distant organs. In addition, cancer cells may undergo the epithelial-mesenchymal transition through the internalization of EVs secreted by stromal cells. In patients with diabetes, adipocyte-derived EVs can regulate gene expression in distant tissues (e.g., the liver) to regulate metabolism. Adipose tissue macrophages in obese mice can secrete EV-containing microRNAs, which lead to insulin resistance and glucose intolerance at both the cellular and systemic levels. In Alzheimer’s disease and Parkinson’s disease, neurocytes release EVs containing disease-related proteins that play important roles in disease progression and transmission. In viral infectious diseases, EVs derived from virus-infected cells can deliver pathogens or certain elements to other cells to mediate transmission.