MP85-02 OVEREXPRESSION OF VCAN IS ASSOCIATED WITH METASTASIS AND UNFAVORABLE PROGNOSIS IN PATIENTS WITH RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology II1 Apr 2016MP85-02 OVEREXPRESSION OF VCAN IS ASSOCIATED WITH METASTASIS AND UNFAVORABLE PROGNOSIS IN PATIENTS WITH RENAL CELL CARCINOMA Yozo Mitsui, Hiroaki Shiina, Shinichiro Fukuhara, Miho Hiraki, Naoko Arichi, Hiroaki Yasumoto, Rajvir Dahiya, and Yuichiro Tanaka Yozo MitsuiYozo Mitsui More articles by this author , Hiroaki ShiinaHiroaki Shiina More articles by this author , Shinichiro FukuharaShinichiro Fukuhara More articles by this author , Miho HirakiMiho Hiraki More articles by this author , Naoko ArichiNaoko Arichi More articles by this author , Hiroaki YasumotoHiroaki Yasumoto More articles by this author , Rajvir DahiyaRajvir Dahiya More articles by this author , and Yuichiro TanakaYuichiro Tanaka More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2268AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The supportive stroma around a solid tumor consists of specific extracellular matrix components, and plays important roles for activating the microenvironment of primary and secondary tumor sites. Versican (VCAN), a large aggregating chondroitin sulfate proteoglycan, is secreted into the extracellular environment. VCAN promotes tumor progression and enhances metastasis in several cancers, and we hypothesized that overexpression of VCAN is associated with the pathogenesis of renal cell carcinoma (RCC). METHODS The expression of VCAN was analyzed using 3 renal tumor cell lines (Caki-2, ACHN, 786-O), and 84 matched clear cell RCC and normal renal tissues. We also examined whether down-regulation of VCAN had an effect on the viability, or migratory and invasion properties of RCC cells. RESULTS The mRNA expression of VCAN in the RCC cell lines was significantly higher than in the nonmalignant HK-2 cell line and also significantly higher in RCC samples as compared to normal kidney samples (p<0.001). The higher expression of VCAN was significantly correlated with systematic metastasis (p<0.001). When the expression level of the VCAN mRNA transcript was divided into 2 groups based on median values, higher expression was significantly associated with 5-year cause-specific survival after radical nephrectomy (p<0.05). After transfection of VCAN siRNA, cell viability, migration, and invasion ability were significantly inhibited in the RCC cell lines. We further analyzed genes affected by VCAN knockdown based on gene microarray and observed that TNF-alpha was up-regulated and MMP7 and CXCR4 were down-regulated. CONCLUSIONS VCAN expression is up-regulated in RCC and associated with poor prognosis. VCAN depletion reduces tumorigenesis in RCC cell lines by inducing TNF-alpha-mediated apoptosis. In addition, VCAN can promote RCC development and metastasis by inducing MMP7 and CXCR4 expression. Thus, VCAN may be an attractive target for novel diagnostic and therapeutic strategies for RCC. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1098 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Yozo Mitsui More articles by this author Hiroaki Shiina More articles by this author Shinichiro Fukuhara More articles by this author Miho Hiraki More articles by this author Naoko Arichi More articles by this author Hiroaki Yasumoto More articles by this author Rajvir Dahiya More articles by this author Yuichiro Tanaka More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...