362 ROLE OF SECRETED FRIZZLED-RELATED PROTEIN 3 (SFRP3) IN HUMAN RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research III1 Apr 2010362 ROLE OF SECRETED FRIZZLED-RELATED PROTEIN 3 (SFRP3) IN HUMAN RENAL CELL CARCINOMA Hiroshi Hirata, Yuji Hinoda, Koji Ueno, Shahana Majid, Sharanjot Saini, Peter Carroll, and Rajvir Dahiya Hiroshi HirataHiroshi Hirata San Francisco, CA More articles by this author , Yuji HinodaYuji Hinoda Ube, Japan More articles by this author , Koji UenoKoji Ueno San Francisco, CA More articles by this author , Shahana MajidShahana Majid San Francisco, CA More articles by this author , Sharanjot SainiSharanjot Saini San Francisco, CA More articles by this author , Peter CarrollPeter Carroll San Francisco, CA More articles by this author , and Rajvir DahiyaRajvir Dahiya San Francisco, CA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.429AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Wnt/beta-catenin signaling is involved in renal cancer. Canonical Wnt ligands bind to frizzled (FZD) family receptors and the LRP5/LRP6 co-receptor, which stabilize beta-catenin. Among Wnt antagonist families, sFRP3 is generally thought to be an inhibitor of Wnt signaling in several cancers. However, sFRP2, which is also a member of the sFRP family, has been previously reported to be involved in oncogenic function in human glioma cells. Here we reported the functional significance of sFRP3 in renal cell carcinoma. METHODS We performed immunohistochemistry on kidney tissue microarray and confirmed the expression level of sFRP3 in normal kidney and renal cancer cell lines (primary and metastatic). We transfected sFRP3 to the primary renal cancer cell lines and performed several functional analysis (MTS, colony formation, apoptosis, cell cycle, invasion, angiogenesis, and in vivo study). We also knocked down sFRP3 mRNA in metastatic cell lines using siRNA technique and performed several functional analysis. Besides we profiled cell cycle, apoptosis, and invasion related genes with microarray. RESULTS We found the level of sFRP3 protein was high in normal kidney, low in primary renal cancer tissues and high in metastatic renal cancer tissues. We performed dual sFRP3 mRNA expression experiments to determine the role of sFRP3 using primary and metastatic renal cancer cell lines. Functional analysis showed increased numbers of viable and invaded cells, tube formation and decreased numbers of apoptotic cells in sFRP3 transfected A498 cells. Promotion of tumor growth was also observed in nude mice injected with sFRP3 transfected A498 cells. In contrast, the number of viable cells and invasive cells was decreased in sFRP3 mRNA knocked down metastatic cells (ACHN and Hs891.T). To investigate the mechanism of sFRP3 function, we performed microarray analysis to see which genes were up or down regulated by sFRP3 expression. Among these genes, MMP-3 and ANGPT1 were significantly up-regulated in sFRP3 transfected cells. CONCLUSIONS This is the first report to show that sFRP3 expression promotes cell growth, invasion, and inhibition of apoptosis in renal cancer cells. Furthermore, our results suggest that sFRP3 may play a role in invasion and angiogenesis by enhancing MMP-3 and ANGPT1 expression. The changes in sFRP3 expression levels in normal, primary cancer, and metastatic renal cancer tissues suggest that sFRP3 may play dual roles as a tumor suppressor gene and an oncogene during renal cancer progression. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e143-e144 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hiroshi Hirata San Francisco, CA More articles by this author Yuji Hinoda Ube, Japan More articles by this author Koji Ueno San Francisco, CA More articles by this author Shahana Majid San Francisco, CA More articles by this author Sharanjot Saini San Francisco, CA More articles by this author Peter Carroll San Francisco, CA More articles by this author Rajvir Dahiya San Francisco, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...