12. Relevance of iNOS expression and nitric oxide production in the maintenance of cancer stem cells in a murine bladder cancer model

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; Reunión Conjunta de Sociedades Biomédicas; 2017

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA

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 in the urothelium and 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 cancer aggressiveness, chemoresistance and relapse. Nitric oxide (NO) is a free radical produced by enzymes called 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 bladder cancer, 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 of NO in CSC maintenance, modulating it production, using pharmacological inhibitors or silencing iNOS expression in a murine BC model.Results: The number of CSCs, determined as spheres forming efficiency (SFE), generated by MB49-I (MI BC cell line) resulted higher than the NMI MB49 line (p