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• W2092248841 abstract "No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Aug 2003Bacillus Calmette-Guerin Initiates Intracellular Signaling in a Transitional Carcinoma Cell Line by Cross-Linking α5β1 Integrin FANGHONG CHEN, GUANGJIAN ZHANG, YOSHIKI IWAMOTO, and WILLIAM A. SEE FANGHONG CHENFANGHONG CHEN More articles by this author , GUANGJIAN ZHANGGUANGJIAN ZHANG More articles by this author , YOSHIKI IWAMOTOYOSHIKI IWAMOTO More articles by this author , and WILLIAM A. SEEWILLIAM A. SEE Financial interest and/or other relationship with Astra Zeneca, Intuitive Surgical, Pfizer, TAP, National Cancer Institute, Southwest Oncology Group, MCW Cancer Center, Veterans Affairs Merit Review, VW Subcontract, NML Foundation, Angigenics, National Institute of Arthritis, Diabetes and Digestive and Kidney Diseases, Abbott, Omnicare/Sepracor and Endocare. More articles by this author View All Author Informationhttps://doi.org/10.1097/01.ju.0000067623.43110.4cAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The adherence of bacillus Calmette-Guerin (BCG) to the surface of transitional carcinoma tumor cells initiates nuclear factor (NF)-κB signal transduction pathways that modulate the expression of proteins important in the antitumor response to BCG. We tested the hypothesis that BCG initiates NF-κB signaling as a consequence of cross-linking α5β1 integrin receptors present on the tumor cell surface. Materials and Methods: The effect of α5β1 antibody mediated cross-linking on interleukin (IL)-6 mRNA expression, IL-6 promoter activation and activation of a specific NF-κB reporter construct was determined. A series of reporter constructs containing nonfunctional mutations in the AP-1, NF-IL-6 and NF-κB sites were used to determine the relative importance of these response elements in α5β1 cross-linking mediated activation of the IL-6 promoter. A final series of experiments assessed the role of α5β1 receptor occupancy by fibronectin (FN) in initiating antibody or BCG mediated signaling. Results: Antiα5 and antiβ1 mediated cross-linking of α5β1 integrin initiated NF-κB signaling, IL-6 promoter activation and IL-6 mRNA expression. Deletion mutants demonstrated that α5β1 cross-link initiated, IL-6 promoter transactivation required intact NF-κB and AP-1 response elements. Receptor occupancy by FN was required for BCG but not for antibody initiated signaling. Conclusions: Cross-linking the α5β1 receptor present on the surface of human transitional carcinoma cells lines initiates signal transduction in a manner identical to that observed for BCG. We propose a model in which multiple FN binding sites present on BCG interact with α5β1 receptor bound FN molecules to cross-link α5β1 receptors and initiate intracellular signaling. References 1 : Intravesical therapy for superficial bladder cancer. Semin Urol Oncol2000; 18: 280. Google Scholar 2 : Fibronectin-mediated Calmette-Guerin bacillus attachment to murine bladder mucosa. Requirement for the expression of an antitumor response. J Clin Invest1990; 85: 62. Google Scholar 3 : Intravesical Bacillus Calmette-Guerin therapy for murine bladder tumors: initiation of the response by fibronectin-mediated attachment of Bacillus Calmette-Guerin. Cancer Res1987; 47: 1762. Google Scholar 4 : Characterization of soluble fibronectin binding to Bacille Calmette-Guerin. J Gen Microbiol1989; 135: 2735. Google Scholar 5 : Interleukin-6 production by bladder tumors is upregulated by BCG immunotherapy. J Urol1995; 154: 572. Link, Google Scholar 6 : Cytokine production by the human bladder carcinoma cell line T24 in the presence of bacillus Calmette-Guerin (BCG). Urol Res1993; 21: 349. Google Scholar 7 : Interleukin-6 production by human bladder tumor cell lines is up-regulated by bacillus Calmette-Guerin through nuclear factor κB and AP-1 via an immediate early pathway. J Urol2002; 168: 786. Link, Google Scholar 8 : New perspectives in cell adhesion: RGD and integrins. Science1987; 238: 491. Google Scholar 9 : Autocrine IL-6 production by human transitional carcinoma cells upregulates expression of the α5β1 fibronectin receptor. J Urol2000; 163: 1553. Abstract, Google Scholar 10 : Integrins: a role as cell signaling molecules. Mol Pathol1999; 52: 208. Google Scholar From the Department of Urology (FC, GZ, YI, WAS) and Human and Molecular Genetics Center (YI), Medical College of Wisconsin, Milwaukee, Wisconsin© 2003 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byZhang G, Chen F, Cao Y and See W (2013) Contributors to HMGB1 Release by Urothelial Carcinoma Cells in Response to Bacillus Calmette-GuérinJournal of Urology, VOL. 190, NO. 4, (1398-1403), Online publication date: 1-Oct-2013.Chen F, Zhang G, Cao Y, Wakim B and See W (2012) A Synthetic Polyvalent Ligand for α5β1 Integrin Activates Components of the Urothelial Carcinoma Cell Response to Bacillus Calmette-GuérinJournal of Urology, VOL. 189, NO. 3, (1104-1109), Online publication date: 1-Mar-2013.Guise A, Chen F, Zhang G and See W (2010) The Effects of Physiological Estrogen Concentration on the Immune Response of Urothelial Carcinoma Cells to Bacillus Calmette-GuérinJournal of Urology, VOL. 185, NO. 1, (298-304), Online publication date: 1-Jan-2011.Chen F, Zhang G, Cao Y, Hessner M and See W (2009) MB49 Murine Urothelial Carcinoma: Molecular and Phenotypic Comparison to Human Cell Lines as a Model of the Direct Tumor Response to Bacillus Calmette-GuerinJournal of Urology, VOL. 182, NO. 6, (2932-2937), Online publication date: 1-Dec-2009.Chen F, Zhang G, Cao Y, Payne R and See W (2007) Bacillus Calmette-Guerin Inhibits Apoptosis in Human Urothelial Carcinoma Cell Lines in Response to Cytotoxic InjuryJournal of Urology, VOL. 178, NO. 5, (2166-2170), Online publication date: 1-Nov-2007.ZHANG G, CHEN F, XU Y, CAO Y, CRIST S, McKERROW A, IWAMOTO Y and SEE W (2018) AUTOCRINE OVER EXPRESSION OF FIBRONECTIN BY HUMAN TRANSITIONAL CARCINOMA CELLS IMPAIRS BACILLUS CALMETTE-GUERIN ADHERENCE AND SIGNALINGJournal of Urology, VOL. 172, NO. 4 Part 1, (1496-1500), Online publication date: 1-Oct-2004. Volume 170Issue 2August 2003Page: 605-610 Advertisement Copyright & Permissions© 2003 by American Urological Association, Inc.Keywordsintegrin alpha5beta1bladder neoplasmsbladderinterleukin-6Mycobacterium bovisMetricsAuthor Information FANGHONG CHEN More articles by this author GUANGJIAN ZHANG More articles by this author YOSHIKI IWAMOTO More articles by this author WILLIAM A. SEE Financial interest and/or other relationship with Astra Zeneca, Intuitive Surgical, Pfizer, TAP, National Cancer Institute, Southwest Oncology Group, MCW Cancer Center, Veterans Affairs Merit Review, VW Subcontract, NML Foundation, Angigenics, National Institute of Arthritis, Diabetes and Digestive and Kidney Diseases, Abbott, Omnicare/Sepracor and Endocare. More articles by this author Expand All Advertisement PDF downloadLoading ..." @default.
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