1354 CHEMOKINE SDF1-B AND RECEPTOR CXCR7: FUNCTIONALLY ASSOCIATED MOLECULAR MARKERS FOR BLADDER CANCER DIAGNOSIS AND PROGNOSIS

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research1 Apr 20111354 CHEMOKINE SDF1-B AND RECEPTOR CXCR7: FUNCTIONALLY ASSOCIATED MOLECULAR MARKERS FOR BLADDER CANCER DIAGNOSIS AND PROGNOSIS Obi Ekwenna, Travis Yates, Miguel Gosalbez, Soum Lokeshwar, Samir Shirodkar, Murugesan Manoharan, Mark Soloway, and Vinata Lokeshwar Obi EkwennaObi Ekwenna Miami, FL More articles by this author , Travis YatesTravis Yates Miami, FL More articles by this author , Miguel GosalbezMiguel Gosalbez Miami, FL More articles by this author , Soum LokeshwarSoum Lokeshwar Miami, FL More articles by this author , Samir ShirodkarSamir Shirodkar Miami, FL More articles by this author , Murugesan ManoharanMurugesan Manoharan Miami, FL More articles by this author , Mark SolowayMark Soloway Miami, FL More articles by this author , and Vinata LokeshwarVinata Lokeshwar Miami, FL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1176AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Inflammatory chemokines and cytokines promote cancer growth and metastasis. Stroma-derived factor SDF-1 is a chemokine that binds to CXCR4 and CXCR7; the two membrane G-protein linked receptors. Six splice variants of SDF1 are known. Very few studies have examined CXCR7 and SDF-1 expression in cancer and none have been conducted in bladder cancer (BCa). We examined the expression of SDF1 splice variants a and b and of CXCR4 and CXCR7 in bladder tissues and in urine specimens and evaluated CXCR4 and CXCR7 function in BCa cell lines. METHODS BCa tissues (n=44) were collected from patients undergoing surgery. Normal bladder (NBL, n=28) tissues were collected from organ donors or at the time of cystectomy. Urine specimens were collected from 186 study individuals (BCa = 57; normal = 27; benign urologic conditions = 55; history of BCa: 30, other cancers = 17). RNA was isolated from tissues and exfoliated cells and subjected to real time RT-PCR for SDF1 (a and b), CXCR4 and CXCR7. CXCR4 and CXCR7 protein expression in tissues was evaluated by immunohistochemistry. CXCR4 and CXCR7 functions in BCa cell lines were examined by siRNA transfection. RESULTS CXCR7 and SDF1 b levels were 7-8-fold elevated in BCa tissues (CXCR7: 3.0 +/− 2.2; SDF1-b: 1.22 +/− 0.39) when compared to NBL tissues (P < 0.0001); CXCR4 and SDF1 a levels did not change significantly. CXCR7 staining increased in BCa tissues (189 +/− 97.7) when compared to NBL tissues (28 +/− 37.7; P < 0.001). In multivariate analysis CXCR7 mRNA levels was an independent prognostic indicator for metastasis (P=0.024; RR: 1.72) and CXCR7 staining independently associated with disease specific mortality (P = 0.038). Urinary CXCR7 mRNA levels had high sensitivity (80.7%; high-grade BCa: 92.3%) and specificity (75.9%) to detect BCa. The SDF1 a/b ratio had 100% sensitivity and 83.4% specificity to detect BCa. While over expression of CXCR7 promoted cell growth and chemotactic motility of BCa cells, its down regulation by siRNA inhibited both functions. CXCR7 overexpression increased EGF-receptor phosphorylation/activation. CONCLUSIONS CXCR7 expression is up-regulated in BCa and correlates with BCa metastasis. CXCR7 promotes BCa growth and chemotactic motility through EFGR activation. SDF1 b/a ratio may be a sensitive marker for BCa detection and promote BCa growth and progression. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e540-e541 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Obi Ekwenna Miami, FL More articles by this author Travis Yates Miami, FL More articles by this author Miguel Gosalbez Miami, FL More articles by this author Soum Lokeshwar Miami, FL More articles by this author Samir Shirodkar Miami, FL More articles by this author Murugesan Manoharan Miami, FL More articles by this author Mark Soloway Miami, FL More articles by this author Vinata Lokeshwar Miami, FL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...