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

Kentaro Jingushi, Motohide Uemura, Naomi Ohnishi, Wataru Nakata, Kazutoshi Fujita, Takuya Naito, Risa Fujii, Naomi Saichi, Norio Nonomura, Kazutake Tsujikawa, Koji Ueda

International journal of cancer 2018 Feb 01

filter terms:

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. © 2017 UICC.

Citation

Kentaro Jingushi, Motohide Uemura, Naomi Ohnishi, Wataru Nakata, Kazutoshi Fujita, Takuya Naito, Risa Fujii, Naomi Saichi, Norio Nonomura, Kazutake Tsujikawa, Koji Ueda. Extracellular vesicles isolated from human renal cell carcinoma tissues disrupt vascular endothelial cell morphology via azurocidin. International journal of cancer. 2018 Feb 01;142(3):607-617