title: Versican Promotes Tumor Progression, Metastasis and Predicts Poor Prognosis in Renal Carcinoma.
abstract: The proteoglycan versican (VCAN) promotes tumor progression and enhances metastasis in several cancers; however, its role in clear cell renal cell carcinoma (ccRCC) remains unknown. Recent evidence suggests that VCAN is an important target of chromosomal5qgain, one of the most prevalent genetic abnormalities in ccRCC. Thus, we investigated whether VCAN expression is associated with the pathogenesis of ccRCC. VCAN expression was analyzed using three RCC and normal kidney cell lines as well as a clinical cohort of 84 matched ccRCC and normal renal tissues. Functional analyses on growth and progression properties were performed using VCAN-depleted ccRCC cells. Microarray expression profiling was employed to investigate the target genes and biologic pathways involved in VCAN-mediated ccRCC carcinogenesis. ccRCC had elevated VCAN expression in comparison with normal kidney in both cell lines and clinical specimens. The elevated expression of VCAN was significantly correlated with metastasis (P< 0.001) and worse 5-year overall survival after radical nephrectomy (P= 0.014).In vitro, VCAN knockdown significantly decreased cell proliferation and increased apoptosis in Caki-2 and 786-O cells, and this was associated with alteration of several TNF signaling-related genes such asTNFα, BID, andBAKFurthermore, VCAN depletion markedly decreased cell migration and invasion which correlated with reduction of MMP7 and CXCR4. These results demonstrate that VCAN promotes ccRCC tumorigenesis and metastasis and thus is an attractive target for novel diagnostic, prognostic, and therapeutic strategies.Implications:This study highlights the oncogenic role of VCAN in renal cell carcinogenesis and suggests that this gene has therapeutic and/or biomarker potential for renal cell cancer.Mol Cancer Res; 15(7); 884-95. ©2017 AACR.
authors.affiliation: Department of Urology, Shimane University Faculty of Medicine, Izumo, Japan. mitsui@med.shimane-u.ac.jp Yuichiro.tanaka@ucsf.edu.|Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California.|Department of Urology, University of California, San Francisco, California.
authors.forename: Yozo
authors.initials: Y
authors.lastname: Mitsui
authors.affiliation: Department of Urology, Shimane University Faculty of Medicine, Izumo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shiina
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California.|Department of Urology, University of California, San Francisco, California.
authors.forename: Taku
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California.|Department of Urology, University of California, San Francisco, California.
authors.forename: Shigekatsu
authors.initials: S
authors.lastname: Maekawa
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California.|Department of Urology, University of California, San Francisco, California.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California.|Department of Urology, University of California, San Francisco, California.
authors.forename: Marisa
authors.initials: M
authors.lastname: Shiina
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California.|Department of Urology, University of California, San Francisco, California.
authors.forename: Mitsuho
authors.initials: M
authors.lastname: Imai-Sumida
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California.|Department of Urology, University of California, San Francisco, California.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Kulkarni
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California.|Department of Urology, University of California, San Francisco, California.
authors.forename: Pritha
authors.initials: P
authors.lastname: Dasgupta
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California.
authors.forename: Ryan Kenji
authors.initials: RK
authors.lastname: Wong
authors.affiliation: Department of Urology, Shimane University Faculty of Medicine, Izumo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Hiraki
authors.affiliation: Department of Urology, Shimane University Faculty of Medicine, Izumo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Arichi
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Fukuhara
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California.|Department of Urology, University of California, San Francisco, California.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yamamura
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California.|Department of Urology, University of California, San Francisco, California.
authors.forename: Shahana
authors.initials: S
authors.lastname: Majid
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California.|Department of Urology, University of California, San Francisco, California.
authors.forename: Sharanjot
authors.initials: S
authors.lastname: Saini
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California.|Department of Urology, University of California, San Francisco, California.
authors.forename: Guoren
authors.initials: G
authors.lastname: Deng
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California.|Department of Urology, University of California, San Francisco, California.
authors.forename: Rajvir
authors.initials: R
authors.lastname: Dahiya
authors.affiliation: Department of Urology, Toho University Faculty of Medicine, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California. mitsui@med.shimane-u.ac.jp Yuichiro.tanaka@ucsf.edu.|Department of Urology, University of California, San Francisco, California.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics*; D011379:Prognosis; D046888:Tissue Array Analysis; D053675:Versicans / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D053675:Versicans