MP28-15 HYAL4: A NEW HYALURONIDASE ASSOCIATED WITH BLADDER CANCER DIAGNOSIS AND PROGNOSIS

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research II1 Apr 2014MP28-15 HYAL4: A NEW HYALURONIDASE ASSOCIATED WITH BLADDER CANCER DIAGNOSIS AND PROGNOSIS John Shields, Soum Lokeshwar, Kelly Hoye, Travis Yates, Murugesan Manoharan, and Vinata Lokeshwar John ShieldsJohn Shields More articles by this author , Soum LokeshwarSoum Lokeshwar More articles by this author , Kelly HoyeKelly Hoye More articles by this author , Travis YatesTravis Yates More articles by this author , Murugesan ManoharanMurugesan Manoharan More articles by this author , and Vinata LokeshwarVinata Lokeshwar More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.664AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The Hyaluronidase (HAase) family of enzymes degrade hyaluronic acid (HA). In the human genome there are 6 HAase genes clustered on chromosomes 3p21.3 (HYAL-1, -2, -3) and 7q31.3 (HYAL-4, PH20, HYALP1). While PH20 and HYAL-2 are testicular and lysosomal HAases, HYAL1 is the tumor-derived HAase. HYLA1 promotes tumor growth, invasion and angiogenesis and is a diagnostic and prognostic marker for bladder cancer (BCa). The expression of other HAases has not been investigated in either normal cells or tumor cells and tissues. In this study we examined the expression of all 6 HAases in bladder tissues, cells and urine. METHODS By real time RT-PCR we examined the mRNA levels of 6 HAase genes in BCa cell lines, 59 bladder tissues (normal (NBL) = 22; tumor (TBL) = 37) and 160 urine specimens (BCa = 52; normal = 18; history of BCa = 30; benign conditions = 59). The levels were normalized to β-actin. HYAL4 function was analyzed by stably overexpressing HYAL4 in normal urothelial and BCa cells, using cell proliferation, motitlity and invasion assays and immunoblotting and Q-PCR. RESULTS HYAL1, HYAL4 and HYALP1 mRNA levels were significantly (6-13-fold) elevated in TBL tissues (12.5 ± 2.7; 29.7 ± 21.9; 26.7 ± 21.9) when compared to NBL tissues (P<0.001). HYAL3 and PH20 were expressed at 100-fold lower levels. HYAL2 expression was comparable to HYAL1 and HYAL4, but the difference in the expression between NBL and TBL was not significant (P>0.05). cDNA cloning revealed that HYALP1 encodes a non-functional truncated protein. HYAL1, HYAL4 and HYALP1 mRNA levels were also significantly elevated in BCa patients’ urine (P< 0.001). Urinary HYAL4 mRNA levels had higher sensitivity (78.9%) and specificity (86.2%) than to detect BCa. Overexpression of HYAL-4 in normal urothelial and BCa cells significantly promoted invasion and chemotactic motility (> 3-fold). This increase was due to up-regulation of metastasis promoters, including CD44, RHAMM) MMP-9 and β-catenin. CONCLUSIONS This is the first study that shows like HYAL1, HYAL4 is a tumor derived HAase that is exclusively expressed in BCa cells. HYAL4 may be a potentially accurate marker for BCa diagnosis and may promote BCa growth and progression. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e301-e302 Advertisement Copyright & Permissions© 2014MetricsAuthor Information John Shields More articles by this author Soum Lokeshwar More articles by this author Kelly Hoye More articles by this author Travis Yates More articles by this author Murugesan Manoharan More articles by this author Vinata Lokeshwar More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...