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FGFR3 Down-Regulation is Involved in bacillus Calmette-Guérin Induced Bladder Tumor Growth Inhibition

2015; Lippincott Williams & Wilkins; Volume: 195; Issue: 1 Linguagem: Inglês

10.1016/j.juro.2015.06.093

1527-3792

Yanina Langle, Denise Belgorosky, Bárbara Prack McCormick, Ana Sahores, Adrián Góngora, Alberto Baldi, Claudia Lanari, Caroline A. Lamb, Ana María Eiján,

Bladder and Urothelial Cancer Treatments

No AccessJournal of UrologyInvestigative Urology1 Jan 2016FGFR3 Down-Regulation is Involved in bacillus Calmette-Guérin Induced Bladder Tumor Growth Inhibition Yanina V. Langle, Denise Belgorosky, Bárbara Prack McCormick, Ana Sahores, Adrián Góngora, Alberto Baldi, Claudia Lanari, Caroline Lamb, and Ana M. Eiján Yanina V. LangleYanina V. Langle , Denise BelgoroskyDenise Belgorosky , Bárbara Prack McCormickBárbara Prack McCormick , Ana SahoresAna Sahores , Adrián GóngoraAdrián Góngora , Alberto BaldiAlberto Baldi , Claudia LanariClaudia Lanari , Caroline LambCaroline Lamb , and Ana M. EijánAna M. Eiján View All Author Informationhttps://doi.org/10.1016/j.juro.2015.06.093AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Bacillus Calmette-Guérin is the standard treatment for patients with nonmuscle invasive high histological grade bladder cancer. Previously we found that bacillus Calmette-Guérin induces murine bladder cancer MB49 cell death in vitro and in vivo, generating tissue remodeling, which involves the release of fibroblast growth factor (FGF)-2. Materials and Methods: We studied the effect of bacillus Calmette-Guérin treatment on FGF-2 and FGF receptor (FGFR) expression in bladder cancer. Results: In vitro FGF-2 increased MB49 cell proliferation but did not reverse bacillus Calmette-Guérin induced cell death. Increased FGF-2 expression was detected after bacillus Calmette-Guérin treatment. Moreover MB49 cells expressed high FGFR3 levels, which decreased after treatment. Similar results were observed in human T24 bladder cancer cells. In vivo MB49 tumors expressed higher FGFR3 levels than normal urothelium. Tumor FGFR3 decreased after treatment and correlated with tumor growth inhibition in response to bacillus Calmette-Guérin. In a pilot bioassay using 11 human bladder tumors treated ex vivo with bacillus Calmette-Guérin we found a subgroup of 41% of patients in whom FGFR3 was decreased after treatment. Conclusions: Based on bladder cancer murine model results we infer that down-regulation of FGFR3 is a predictive marker of a good response to bacillus Calmette-Guérin therapy. The decrease in FGFR3 in response to bacillus Calmette-Guérin occurred not only in a murine model but also in a human bladder cancer cell line and in some patient samples. More patients and increased followup are needed to establish the predictive role of FGFR3 as a marker in human bladder cancer. References 1 : Global cancer statistics. CA Cancer J Clin2011; 61: 69. Google Scholar 2 : Tumours of the urinary system. In: Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs. World Health Organization Classification of Tumours. Lyon: IARC2004: 89. 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Volume 195Issue 1January 2016Page: 188-197 Advertisement Copyright & Permissions© 2016 by American Urological Association Education and Research, Inc.Keywordsreceptors, fibroblast growth factorfibroblast growth factorsBCG vaccineurinary bladder neoplasmsbiological markersAcknowledgmentsDr. Leonardo Pasik, Department of Urology, Roffo Institute, assisted with the study. Dr. Claudia Arguelles, Instituto Nacional de Produccion de Biologicos, provided BCG. Dr. Dante Paz, Faculty of Nature Sciences, University of Buenos Aires, assisted with confocal microscopy. Lic. Inés Kletzky reviewed the English. Alberto Baldi developed FGF-2 and FGF-2 blocking antibody DB3.MetricsAuthor Information Yanina V. Langle No direct or indirect commercial incentive associated with publishing this article. More articles by this author Denise Belgorosky Financial interest and/or other relationship with Consejo Nacional de Investigaciones Científicas y Técnicas. More articles by this author Bárbara Prack McCormick Financial interest and/or other relationship with Consejo Nacional de Investigaciones Científicas y Técnicas. More articles by this author Ana Sahores Financial interest and/or other relationship with Consejo Nacional de Investigaciones Científicas y Técnicas. More articles by this author Adrián Góngora Financial interest and/or other relationship with Consejo Nacional de Investigaciones Científicas y Técnicas. More articles by this author Alberto Baldi Financial interest and/or other relationship with Consejo Nacional de Investigaciones Científicas y Técnicas. More articles by this author Claudia Lanari Financial interest and/or other relationship with Consejo Nacional de Investigaciones Científicas y Técnicas. More articles by this author Caroline Lamb Financial interest and/or other relationship with Consejo Nacional de Investigaciones Científicas y Técnicas. More articles by this author Ana M. Eiján Financial interest and/or other relationship with Consejo Nacional de Investigaciones Científicas y Técnicas. More articles by this author Expand All Advertisement PDF downloadLoading ...