Small extracellular vesicles promote the formation of the pre-metastatic niche through multiple mechanisms in colorectal cancer.

Colorectal cancer (CRC) ranks among the most prevalent global malignancies, posing significant threats to human life and health due to its high recurrence and metastatic potential. Small extracellular vesicles (sEVs) released by CRC play a pivotal role in the formation of the pre-metastatic niche (PMN) through various mechanisms, preparing the groundwork for accelerated metastatic invasion. This review systematically describes how sEVs promote CRC metastasis by upregulating inflammatory factors, promoting immunosuppression, enhancing angiogenesis and vascular permeability, promoting lymphangiogenesis and lymphatic network remodeling, determining organophilicity, promoting stromal cell activation and remodeling and inducing the epithelial-to-mesenchymal transition (EMT). Furthermore, we explore potential mechanisms by which sEVs contribute to PMN formation in CRC and propose novel insights for CRC diagnosis, treatment, and prognosis.