Relevance of iNOS expression and nitric oxide production in the maintenance of cancer stem cells in bladder cancer

DENISE BELGOROSKY; YANINA LANGLE, ; JULIE GIROUARD ; JOVANE HAMELIN-MORRISSETE ; CATALINA LODILLINSKY,; NATALIA BALARINO, ; EDUARDO SANDES ; MACARENA ZAMBRANO, ; MARIANELA SCIACCA , ; CARLOS REYES-MORENO; ANA MARIA EIJAN

CIUDAD AUTONOMA DE BUENOS AIRES

Congreso; IV International Congress in Traslational Medicine. 27-28 de Marzo de 2018, FFyB-FMed-UBA; 2018

Introduction: Bladder cancer (BC) is the second most common tumor of the male urogenital tract, and an important worldwide cause of death. BC is classified as no muscle invasive (NMI) when it is localized from the urothelium to the lamina propriaand muscle invasive (MI), when it reaches the detrusor muscle. Increasing evidence has indicated the presence of cancer stem cells (CSCs) in many types of cancers, associated with aggressiveness, chemoresistance and relapse. Nitric oxide (NO) is a free radical produced by enzymes called NO synthases(NOS). The inducible isoform (iNOS) produces high levels of NO in response to inflammatory stimuli. The expression of iNOS in human BC is a poor prognostic factor associated with increased invasion and tumor recurrence. Although there is evidence supporting the role of NO/iNOS in the promotion and progression of BC, the possibility that there are CSCs dependent on endogenous NO generation has not yet been clearly defined.The objective of this study was to evaluate the role ofNO in CSC maintenance, modulating NO production, using pharmacological inhibitors (L-NAME and 1400 W)orsilencingiNOS expression in a murine BC model. Furthermore, we study the expression of CSC markers and iNOS in a pilot study in human BC samples of patients from the Instituto de Oncología A. H Roffo. Results: The number of CSCs, determined as spheres forming efficiency(SFE), generated by MB49-I (MI murineBC cell line) resulted higher than the NMI MB49 line (p