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Extracellular vesicles isolated from human renal cell carcinoma tissues disrupt vascular endothelial cell morphology via azurocidin
Author(s) -
Jingushi Kentaro,
Uemura Motohide,
Ohnishi Naomi,
Nakata Wataru,
Fujita Kazutoshi,
Naito Takuya,
Fujii Risa,
Saichi Naomi,
omura Norio,
Tsujikawa Kazutake,
Ueda Koji
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31080
Subject(s) - extracellular vesicles , renal cell carcinoma , clear cell renal cell carcinoma , cell , extracellular , cancer research , extracellular vesicle , microbiology and biotechnology , vesicle , biology , chemistry , pathology , immunology , medicine , microvesicles , biochemistry , membrane , microrna , gene
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.