3. ROLE OF NITRIC OXIDE IN BREAST TUMOR PROGRESSION

MARIANELA SCIACCA, ; DENISE BELGOROSKY, ; MACARENA ZAMBRANO, ; JOSÉ IGNACIO GÓMEZ ESCALANTE; , FERNANDA ROCA,; YANINA V. LANGLE,; EDUARDO SANDES, ; CATALINA LODILLINSKY; ANA MARIA EIJAN

MAR DEL PLATA

Congreso; Reunión Conjunta de la Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad Argentina de Inmunología (SAI) y la Sociedad Argentina de Fisiología (SAFIS).; 2018

In Argentine, breast cancer is the one with highest incidence in women. Nitric Oxide (NO) is generated by a family of NO synthases (NOS), being the inducible isoform (iNOS) which produces higher NO levels. This, often acts as a survival factor, hence inhibition of iNOS has been proposed as a targeted therapy. Fibroblasts, the main cell type in tumor microenvironment, have been described as a heterogenic population and their role in breast cancer associated to NO inhibition has not been yet elucidated.In this work, using three mouse mammary breast cancer cell lines, the impact of inhibiting NO in tumor progression was evaluated. LM3 and its more aggressive variant LMM3 cell line expressed iNOS. On the other hand, LM2, line did not express iNOS. Consistent with iNOS expression, both LM3 and LMM3 produced NO, which is in¬hibited by L-NAME. When cell viability was evaluated, NO inhibition on iNOS-positive cells induced a reduction in cell viability. The iN¬OS-negative cell line, LM2, did not produce NO and its viability was not affected by L-NAME.In vivo, in parallel with tumor reduction induced by L-NAME, collagen deposition and α-SMA positive stromal cells were identified by histological analyses. These observations take place only when tumor cells express iNOS. (LM3: p