La expresion de S100A9, vinculada con el óxido nítrico, es un marcador de mal pronóstico en pacientes con cáncer de vejiga, siendo su inhibición un posible blanco terapeutico

YANINA LANGLE ; EDUARDO SANDES ; DENISE BELGOROSKY,; NATALIA BALARINO, ; BÁRBARA PRACK MC CORMICK; LINA MARINO ; ERICA ROJAS BILBAO ; HÉCTOR MALAGRINO ; LEONARDO PASIK ; ALBERTO CASABÉ ; ANA MARÍA EIJÁN

REVISTA ARGENTINA DE UROLOGIA (1990)

SOCIEDAD ARGENTINA DE UROLOGÍA

Lugar: Buenos Aires; Año: 2014 vol. 79 p. 64 - 70

0327-3326

Nitric oxide (NO) is produced by the NO synthases (NOS) enzymes. We have previously described that iNOS, the inducible isoform of NOS, was expressed in the 50% of human bladder cancers (BCa). This was associated with tumor recurrence and invasion. Using the murine BCa model MB49 that generate non-muscle invasive bladder tumors (NMI) and that express iNOS, we identified that treatment with LNAME (a NO production inhibitor) reduced S100A9 protein expression. This protein triggers a suppressive immune response through myeloid-derived suppressor cells (MDSC)recruitment. Objectives: To evaluate 1) S100A9 expression as a prognostic marker in patients with BCa. 2) Inhibition of NO as a herapeutic target using the murine BCa model, focusing on S100A9 expression, the number of MDSC and tumor growth, with or without BCG treatment. We have identified that S100A9 was expressed in MB49 tumor cells and in the immune cells that infiltrate tumors. We found a positive correlation between iNOS and S100A9 expression in tumor cells, suggesting that its expression would be linked. Invasive tumors have a higher number of immune cells that infiltrate tumors that were positive for S100A9 compared with the NMI tumors (p < 0.05). This immune cells were predominantly monocytes/macrophages (CD14) in the NMI tumors (p