Efecto de BLS en el modelo murino de carcinoma mamario 4T1

GOLDIN CARLA; GIL CAMILA; GOLDBAUM FERNANDO; FARIAS ANA; BERGUER PAULA

Ciudad de Buenos Aires

Jornada; XXXIII Jornadas Multidisciplinarias del Instituto de Oncología Ángel H. Roffo ?Equipo multidisciplinario: el camino obligado en la oncología?; 2018

Instituto de Oncologia Angel H. Roffo

Brucella lumazine synthase (BLS) is a stable homodecameric protein. BLS signaling via Toll-Like Receptor 4 (TLR4) regulates innate and adaptive immune responses, inducing dendritic cell maturation and CD8+ T-cell cytotoxicity. In the B16 melanoma model, BLS delays tumor growth via tumor TLR4 when administered at day 2. In this work, we studied the effect of BLS in the metastatic breast adenocarcinoma 4T1 model. Firstly, we characterized the cell line evaluating the expression of TLR4 in 4T1 cells by flow cytometry. Lower levels of TLR4 were detected on 4T1 cells compared to B16 cells. Different growth curves were analyzed by inoculating different amounts of 4T1 cells s.c. (5,105-1,106 cells) into the mammary gland. Metastases and lung damage were observed in all mice, however tumors were not measurable. In order to evaluate if BLS has an effect in tumor growth, 5x104 4T1 cells were s.c. inoculated in the right flank and 200µg of BLS was administered at day 2. Tumor growth is not affected by BLS. At day 21 tumors were analyzed by flow cytometry and lungs were examined. Lung metastases were seen in both groups. Furthermore, lungs from mice treated with BLS show more damage and reduced size. Regarding to the tumor microenvironment, a higher percentage of CD45+ cells (4,130%±1,498 vs 42,21%±39,27; p