Extracellular vesicles isolated from human renal cell carcinoma tissues disrupt vascular endothelial cell morphology via azurocidin

Cancer‐associated extracellular vesicles (EVs) are intimately involved in establishment of tumor microenvironment and occurrence of metastasis. However, previous studies have mainly relied on experiments with cultured cell lines or mouse models, making it difficult to gain a full understanding of EV functions in human body. Hence, we extracted EVs directly from surgically resected viable clear cell renal cell carcinoma (ccRCC) tissues and adjacent normal renal tissues (n = 20). Quantitative LC/MS analysis identified 3,871 tissue‐exudative EV (Te‐EV) proteins, among which azurocidin (AZU1) was highly enriched in tumor Te‐EVs (p = 2.85 × 10−3, fold‐change = 31.59). Importantly, AZU1 content was also significantly higher in serum EVs from ccRCC patients compared to those from healthy donors. We further found that ccRCC‐derived EVs had AZU1‐dependent membrane permeabilizing activity for the vascular endothelial cell layer. Thus Te‐EVs should be ideal resource for investigation of physiological EV functions. What's new? A number of studies have revealed that extracellular vesicles (EVs) influence major tumor‐related pathways. However, the studies mainly focused on EVs derived from cultured cells, and there is still little data comparing EVs secreted from tumor cells to those from normal cells. The present report marks the first successful isolation and molecular characterization of EVs secreted from fresh viable human tissue specimens (Te‐EVs). Furthermore, azurocidin was highly expressed in tumor‐derived Te‐EVs and identified as a novel permeabilizer for vascular endothelial cells. Integrated omics studies in Te‐EVs may open a new avenue for understanding the physiological functions of EVs in disease.