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

YANINA V. LANGLE ; DENISE BELGOROSKY ,; ANA SAHORES ; ADRIÁN GÓNGORA ; CLAUDIA LANARI ; CAROLINE LAMB ; EIJAN A M; BÁRBARA PRACK MC CORMICK ; ALBERTO BALDI; ANA MARÍA EIJÁN

JOURNAL OF UROLOGY

ELSEVIER SCIENCE INC

Año: 2016 vol. 195 p. 188 - 197

0022-5347

Background: 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).Objective: To study the effect of BCG treatment in FGF-2 and fibroblast growth factor receptors (FGFRs) expression in BC.Results: 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.Conclusion: 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.