837 INDUCTION OF MONOCYTE CHEMOATTRACTANT PROTEIN 1 BY SPHINGOSINE-1-PHOSPHATE IN NEUROBLASTOMA

You have accessJournal of UrologyPediatrics: Stones/Tumors1 Apr 2012837 INDUCTION OF MONOCYTE CHEMOATTRACTANT PROTEIN 1 BY SPHINGOSINE-1-PHOSPHATE IN NEUROBLASTOMA Mei-Hong Li, Timothy Hla, and Fernando Ferrer Mei-Hong LiMei-Hong Li Farmington, CT More articles by this author , Timothy HlaTimothy Hla New York, NY More articles by this author , and Fernando FerrerFernando Ferrer Hartford, CT More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.928AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. It is a highly angiogenic tumor with poor prognosis. Bioactive lipid sphingosine-1-phosphate (S1P) and its five specific receptors (S1P1-5) have been implicated in many pathological processes including tumor growth and progression. However, little is known concerning the role of S1P in NB. Our preliminary data by human angiogenesis array showed that S1P induced the secretion of several angiogenesis-related proteins such as vascular endothelial growth factor (VEGF) as well as monocyte chemoattractant protein 1 (MCP-1/CCL2), an important inflammatory chemokine in NB. Recently, we have shown that S1P/S1P2 signaling mediates VEGF expression and thus promotes NB growth. In the present study, we investigated the mechanism of S1P-induced CCL2 expression in NB. METHODS Quantitative real-time PCR was conducted to detect the mRNA levels of S1PRs and CCL2 in NB SK-N-AS cells and tissues while CCL2 ELISA was utilized to detect the CCL2 protein secretion in SK-N-AS cells treated with/without S1P. Gain and loss of functions studies were performed by specific S1PR antagonists, adenoviral transduction and siRNA transfection. Western blot analysis and quantitative real-time PCR were employed to confirm the efficiency of transfection. RESULTS S1PR1-3 mRNAs were abundantly expressed in NB tissues. In SK-N-AS cells which reproduce this S1PR expression pattern, S1P induced CCL2 mRNA expression and protein secretion in time- and concentration-dependent manners. Blockade of S1P2 signaling using specific S1P2 antagonist JTE-013 inhibited S1P-induced CCL2 secretion. Overexpression of S1P2 by adenoviral transduction into SK-N-AS cells increased CCL2 secretion while knockdown of S1P2 by S1P2 siRNA transfection decreased CCL2 mRNA expression and protein secretion. CONCLUSIONS Taken together, our data for the first time demonstrate that S1P induced CCL2 expression in NB cells via S1P2, which provides the new insights into the complicated functions of S1P2 in cancer. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e341 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mei-Hong Li Farmington, CT More articles by this author Timothy Hla New York, NY More articles by this author Fernando Ferrer Hartford, CT More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...