BACILLUS CALMETTE-GUERIN (BCG) REGULATES THE EXPRESSION OF FIBROBLAST GROWTH FACTOR RECEPTOR 3 (FGFR3) ASSOCIATED WITH CELL VIABILITY IN BLADDER CANCER. DEVELOPMENT OF A RESPONSE BIOASSAY

YANINA LANGLE, ; DENISE BELGOROSKY, ; MACARENA ZAMBRANO,; MARIANELA SCIACCA,; EDUARDO IMANOL AGÜERO, ; HECTOR MALAGRINO, ; MARIANO BRZEZINSKI, ; EDUARDO SANDES, ; ANA MARIA EIJAN

MAR DEL PLATA

Congreso; Reunión Conjunta de la Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad Argentina de Inmunología (SAI) y la Sociedad Argentina de Fisiología (SAFIS).; 2018

Bacillus Calmette-Guerin (BCG) is the standard treatment for high-grade non-muscle invasive (NMI) bladder cancer (BC). Using a mu¬rine orthotopic BC model we demonstrated that BCG induces tumor growth inhibition, associated with FGFR3 down-regulation. Objec¬tive: a) to study the relationship between FGFR3 expression and cell viability in response to BCG in human BC cell lines; b) to analyze, in human BC samples, FGFR3 modulation by BCG and to evaluate its association with patient outcome.Mat & Met: a) Human BC cell lines were treated with +/-BCG. Viabil¬ity was assessed by MTS and FGFR3 expression by qPCR. b) Bio¬assay: Cells from human bladder tumors (n=41) were divided in two sub-cultures: 1-FGFR3 basal expression; 2-FGFR3 BCG-treated.Results: a) BCG increased FGFR3 expression and viability in RT4 and 5637 while were reduced in T24 and UMUC6. In J82, BCG di¬minished viability without modified FGFR3 expression. The reduc¬tion in cell viability observed was associated with the activation of pro-apoptotic protein Cathepsin B. b) Bioassay: BCG induced re¬duction or no variation of FGFR3 expression in 59% of samples (17/41), been 44% low-grade and 64% high-grade NMI tumors; and 75% (9/12) invasive tumors. Five patients were treated with BCG: two reduced FGFR3 expression and remained free of disease for more than 2 years. Three patients presented FGFR3 increased, pro¬gressing in their disease ending in radical cystectomy.Conclusion: FGFR3 variations are related to BC cell viability and could be used as a predictive marker of response to BCG therapy. This modulation occurs in near 60% of patient tumor samples ana¬lyzed, appearing to be associated to therapeutic response. A large number of high-grade NMI tumor samples and the follow-up of those patients will be necessary to establish the predictive role of FGFR3 and the usefulness of our bioassay as a marker of response to BCG treatment.