Importance of iNOS expression in bladder cancer stem cells.

BELGOROKY DENISE; LANGLE, YANINA VERONICA ; GIROUARD JULIE ; HAMELIN-MORRISSETE JOVANE; MARINO, LINA ; AGUERO, EDUARDO IMANOL; MALAGRINO, HECTOR; ; REYES-MORENO, CARLOS ; EIJAN ANA MARIA.

Congreso; AACR ANNUAL MEETING 2021; 2021

AACR

Abstract AACR 2021 AACR ANNUAL MEETING 2021-Virtual Meeting- April 10-15;Authors: Belgorosky, Denise1; Langle, Yanina Veronica1; Girouard, Julie2; Hamelin-Morrissete, Jovane2, Marino, Lina3; Aguero, Eduardo Imanol1; Malagrino, Hector4; Reyes-Moreno, Carlos2; Eiján, Ana María1.Title: Importance of iNOS expression in bladder cancer stem cellsShort title: iNOS expression in bladder CSCBackground: Bladder cancer (BC) is the second most common tumor of the male urogenital tract, and an important worldwide cause of death. Increasing evidence has indicated the presence of cancer stem cells (CSCs) in many types of cancers, associated with cancer aggressiveness, chemoresistance and relapse. The expression of inducible nitric oxide (NO) synthase (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. In this study we evaluate the role of NO in CSC maintenance, modulating it production, using pharmacological inhibitors or silencing iNOS expression in a murine BC model. Also, we analyzed iNOS expression in correlation with CSC markers in human BC samples, with different invasion grade. Methods: iNOS pharmacological inhibitors (NOS inhibitor, and iNOS specific inhibitor) or shRNA were used on murine BC model with different iNOS expression and invasiveness grade: MB49 (iNOS+, non-muscle invasive (NMI)) and MB49-I (iNOS++, muscle invasive (MI)), in order to analyze cell proliferation, tumor growth, number of CSC, and pluripotential markers expression. iNOS expression and pluripotential markers were also analyzed in human BC samples by qPCR.Results: The number of CSCs, determined as spheres forming efficiency (SFE), generated by MB49-I resulted higher than NMI MB49 line (p