FGFR3 down-regulation is involved in BCG-induced bladder tumor growth inhibition

Bacillus Calmette-Guerin (BCG) is the standard treatment for patients with non-muscle invasive high histological grade bladder cancer (BC). Previously, we have demonstrated that BCG induces murine BC MB49 cell death both in vitro and in vivo, generating tissue remodeling, which involves the release of fibroblast growth factor 2 (FGF-2).

To study the effect of BCG treatment in FGF-2 and fibroblast growth factor receptors (FGFRs) expression in BC

In vitro, FGF-2 increased MB49 cell proliferation, but was not able to reverse BCG-induced cell death An increased expression of FGF-2 was detected after BCG treatment Moreover, MB49 cells expressed high FGFR3 levels, which decreased after BCG treatment Similar results were observed in human T24 BC cells In vivo, MB49 tumors expressed higher FGFR3 levels than normal urothelium Tumor FGFR3 decreased after treatment and correlates with tumor growth inhibition in response to BCG In a pilot bioassay using human bladder tumors (n=11) treated ex vivo with BCG, we found a sub-group of patients (41%) where FGFR3 was reduced after treatment

Based on BC murine model results, we can infer that the down-regulation of FGFR3 is a predictive marker of good response for BCG therapy The decrease of FGFR3 in response to BCG occurs not only in the murine model but also in a human BC cell line and in some patient samples Both, the increase of patients and their follow-up are necessary to establish the predictive role of FGFR3 as a marker in human BC

The Journal of urology 2015 Jul 02 [Epub ahead of print]

Yanina V Langle, Denise Belgorosky, Bárbara Prack Mc Cormick, Ana Sahores, Adrián Góngora, Alberto Baldi, Claudia Lanari, Caroline Lamb, Ana M Eiján

Área de Investigación, Instituto de Oncología "Ángel H Roffo" Universidad de Buenos Aires - Av San Martín 5481, (CP: 1417DTB), Buenos Aires, Argentina , Área de Investigación, Instituto de Oncología "Ángel H Roffo" Universidad de Buenos Aires - Av San Martín 5481, (CP: 1417DTB), Buenos Aires, Argentina , Área de Investigación, Instituto de Oncología "Ángel H Roffo" Universidad de Buenos Aires - Av San Martín 5481, (CP: 1417DTB), Buenos Aires, Argentina , Instituto de Biología y Medicina Experimental (IBYME) - Consejo Nacional de Investigaciones Científicas y Técnicas a (CONICET), Buenos Aires, Argentina , Instituto de Biología y Medicina Experimental (IBYME) - Consejo Nacional de Investigaciones Científicas y Técnicas a (CONICET), Buenos Aires, Argentina , Instituto de Biología y Medicina Experimental (IBYME) - Consejo Nacional de Investigaciones Científicas y Técnicas a (CONICET), Buenos Aires, Argentina , Instituto de Biología y Medicina Experimental (IBYME) - Consejo Nacional de Investigaciones Científicas y Técnicas a (CONICET), Buenos Aires, Argentina , Instituto de Biología y Medicina Experimental (IBYME) - Consejo Nacional de Investigaciones Científicas y Técnicas a (CONICET), Buenos Aires, Argentina , Área de Investigación, Instituto de Oncología "Ángel H Roffo" Universidad de Buenos Aires - Av San Martín 5481, (CP: 1417DTB), Buenos Aires, Argentina  

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