Research Papers:

Autocrine IL-6 mediates pituitary tumor senescence

Melanie Sapochnik, Mariana R. Haedo, Mariana Fuertes, Pablo Ajler, Guillermo Carrizo, Andrés Cervio, Gustavo Sevlever, Günter K. Stalla and Eduardo Arzt _

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Oncotarget. 2017; 8:4690-4702. https://doi.org/10.18632/oncotarget.13577

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Melanie Sapochnik1,*, Mariana R. Haedo1,*, Mariana Fuertes1, Pablo Ajler2, Guillermo Carrizo2, Andrés Cervio3, Gustavo Sevlever3, Günter K. Stalla4, Eduardo Arzt1,5

1Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA)-CONICET-Partner Institute of the Max Planck Society, Buenos Aires, C1425FQD, Argentina

2Servicio de Neurocirugía, Hospital Italiano, C1199ABD, Buenos Aires, Argentina

3Departamento de Neurocirugía, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), C1428AQK, Buenos Aires, Argentina

4Department of Clinical Research, Max Planck Institute of Psychiatry, Munich, Germany

5Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina

*These authors have contributed equally to this work

Correspondence to:

Eduardo Arzt, email: [email protected]

Keywords: senescence, IL-6, pituitary tumor, benign tumor, autocrine

Received: April 29, 2016    Accepted: November 06, 2016     Published: November 24, 2016


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-β-gal activity and p16INK4a 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-β-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.

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