Autocrine IL-6 mediates pituitary tumor senescence

作者：Sapochnik Melanie; Haedo Mariana R; Fuertes Mariana; Ajler Pablo; Carrizo Guillermo; Cervio Andres; Sevlever Gustavo; Stalla Gunter K; Arzt Eduardo^*

来源：Oncotarget, 2017, 8(3): 4690-4702.

DOI：10.18632/oncotarget.13577

• senescence
• IL-6
• pituitary tumor
• benign tumor
• autocrine

Cellular senescence is a stable proliferative arrest state. Pituitary adenomas are frequent and mostly benign, but the mechanism for this remains unknown. IL-6 is involved in pituitary tumor progression and is produced by the tumoral cells. In a cell autonomous fashion, IL-6 participates in oncogene-induced senescence in transduced human melanocytes. Here we prove that autocrine IL-6 participates in pituitary tumor senescence. Endogenous IL-6 inhibition in somatotroph MtT/S shRNA stable clones results in decreased SA-beta-gal activity and p16(INK4a) but increased pRb, proliferation and invasion. Nude mice injected with IL-6 silenced clones develop tumors contrary to MtT/S wild type that do not, demonstrating that clones that escape senescence are capable of becoming tumorigenic. When endogenous IL-6 is silenced, cell cultures derived from positive SA-beta-gal human tumor samples decrease the expression of the senescence marker. Our results establish that IL-6 contributes to maintain senescence by its autocrine action, providing a natural model of IL-6 mediated benign adenoma senescence.

• 出版日期2017-1-17