Yanina V Langle1, Denise Belgorosky1, Bárbara Prack McCormick1, Ana Sahores1, Adrián Góngora1, Alberto Baldi1, Claudia Lanari1, Caroline Lamb1, Ana M Eiján2. 1. Área de Investigación, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires, Buenos Aires, Buenos Aires, Argentina; Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (AS, AG, AB, CL, CL), Buenos Aires, Buenos Aires, Argentina. 2. Área de Investigación, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires, Buenos Aires, Buenos Aires, Argentina; Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (AS, AG, AB, CL, CL), Buenos Aires, Buenos Aires, Argentina. Electronic address: grupoeijan@gmail.com.
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.
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 murinebladder 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. TumorFGFR3 decreased after treatment and correlated with tumor growth inhibition in response to bacillus Calmette-Guérin. In a pilot bioassay using 11 humanbladder 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 cancermurine 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 humanbladder 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 humanbladder cancer.
Authors: Constance Le Goux; Sophie Vacher; Anne Schnitzler; Nicolas Barry Delongchamps; Marc Zerbib; Michael Peyromaure; Mathilde Sibony; Yves Allory; Ivan Bieche; Diane Damotte; Geraldine Pignot Journal: Sci Rep Date: 2020-10-06 Impact factor: 4.379