Extracellular vesicles in tumor microenvironment modulation and clinical diagnosis

Extracellular vesicles (EVs) are key drivers of tumor metastasis and colonization. Their cargo, consisting of proteins, nucleic acids, and other biomolecules, functions as molecular messengers that trigger the epithelial-mesenchymal transition (EMT) process in tumor cells and facilitate immune evasion by releasing immunosuppressive factors to promote immune escape. Additionally, EVs influence intercellular interactions within the tumor microenvironment, facilitating angiogenesis, increasing vascular permeability, and supplying nutrients and oxygen to support tumor growth and metastasis. During metastasis, EVs protect circulating tumor cells (CTCs) from shear forces in the vascular network and attacks from the immune system. Furthermore, tumor-derived EVs facilitate the establishment of pre-metastatic niches (PMNs), thereby facilitating organ-specific metastasis. In this review, we overview the biogenesis and functions of EVs, as well as various factors that regulate their secretion. We systematically review tumor-derived EV functions in tumor progression, and also the effects of their interactions with other cells (such as adipocytes, immune cells, fibroblasts, and mesenchymal stem cells) in the tumor microenvironment was clarified. Additionally, we evaluate the diagnostic and prognostic potential of EVs as biomarkers for early tumor detection. The review also summarizes validated EV-associated biomarkers, offering a valuable foundation for the development of EV-based strategies in cancer diagnosis and therapy.