Mechanical regulation of extracellular vesicle activity during tumour progression

Extracellular vesicles (EVs) are naturally occurring membrane-bound vesicles secreted by cells. Functionalized with surface-targeting molecules and carrying signalling proteins and nucleic acids as cargo, EVs can rewire pathways and alter biological processes in recipient cells. Tumour-derived EVs have key roles in cancer progression, particularly in metastasis, by promoting tumour cell invasion and the establishment of pre-metastatic niches. An evolving understanding of EVs in cancer highlights a complex intercellular communication network within and beyond the tumour microenvironment that involves cancer cells and non-cancerous cell types, such as fibroblasts and endothelial cells. More recently, EVs have also been recognized for their role in modulating interactions between host and immune cells and in reprogramming the tumour immune microenvironment. In this Review, we discuss EV biogenesis and function in diverse mechanobiological and mechanoimmunological contexts, highlighting how mechanical cues influence EV targeting and activity. The intricate interplay between mechanical forces and EV dynamics contributes to tumour progression and links EVs to key disease hallmarks. This Review discusses how mechanical cues can influence extracellular vesicle targeting and activity.