Autocrine IL-6 mediates pituitary tumor senescence

SAPOCHNIK, M.; HAEDO, M.R.; FUERTES, M.; AJLER, P.; CARRIZO, G.; CERVIO, A.; SEVLEVER, G.; STALLA, G.K.; ARZT, E.

Oncotarget

Impact Journals

Año: 2017 vol. 8 p. 4690 - 4702

1949-2553

Cellular senescence is a stable proliferative arrest state. Pituitary adenomas arefrequent and mostly benign, but the mechanism for this remains unknown. IL-6 isinvolved in pituitary tumor progression and is produced by the tumoral cells. In a cellautonomous fashion, IL-6 participates in oncogene-induced senescence in transducedhuman melanocytes. Here we prove that autocrine IL-6 participates in pituitary tumorsenescence. Endogenous IL-6 inhibition in somatotroph MtT/S shRNA stable clonesresults in decreased SA-β-gal activity and p16INK4a but increased pRb, proliferationand invasion. Nude mice injected with IL-6 silenced clones develop tumors contraryto MtT/S wild type that do not, demonstrating that clones that escape senescence arecapable of becoming tumorigenic. When endogenous IL-6 is silenced, cell culturesderived from positive SA-β-gal human tumor samples decrease the expression of thesenescence marker. Our results establish that IL-6 contributes to maintain senescenceby its autocrine action, providing a natural model of IL-6 mediated benign adenomasenescence.