Miniatura

Fitxers

672394.pdf (1.36 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2017-03-16

Llicència de publicació

cc-by (c) Campillo, Noelia et al., 2017
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/121403

Role of Cyclooxygenase-2 on Intermittent Hypoxia-Induced Lung Tumor Malignancy in a Mouse Model of Sleep Apnea

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1038/srep44693

Resum

An adverse role for obstructive sleep apnea (OSA) in cancer epidemiology and outcomes has recently emerged from clinical and animal studies. In animals, intermittent hypoxia (IH) mimicking OSA promotes tumor malignancy both directly and via host immune alterations. We hypothesized that IH could potentiate cancer aggressiveness through activation of the cyclooxygenase-2 (COX-2) pathway and the concomitant increases in prostaglandin E2 (PGE2). The contribution of the COX-2 in IH-induced enhanced tumor malignancy was assessed using celecoxib as a COX-2 specific inhibitor in a murine model of OSA bearing Lewis lung carcinoma (LLC1) tumors. Exposures to IH accelerated tumor progression with a tumor associated macrophages (TAMs) shift towards a pro-tumoral M2 phenotype. Treatment with celecoxib prevented IH-induced adverse tumor outcomes by inhibiting IH-induced M2 polarization of TAMs. Furthermore, TAMs isolated from IH-exposed mice treated with celecoxib reduced the proliferation of LLC1 naïve cells, while the opposite occurred with placebo-treated IH-exposed mice. Finally, in vitro IH exposures of murine macrophages and LLC1 cells showed that both cell types increased PGE2 release in response to IH. These results suggest a crucial role for the COX-2 signaling pathway in the IH-exacerbated malignant processes, and designate macrophages and lung adenocarcinoma cells, as potential sources of PGE2.

Matèries

Síndromes d'apnea del son, Càncer

Matèries (anglès)

Sleep apnea syndromes, Cancer

Citació

Col·leccions

Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Medicina)

Citació

CAMPILLO, Noelia, TORRES, Marta, VILASECA, Antoni, NONAKA, Paula naomi, GOZAL, David, ROCA I FERRER, Jordi, PICADO VALLÉS, César, MONTSERRAT CANAL, José ma., FARRÉ VENTURA, Ramon, NAVAJAS NAVARRO, Daniel, ALMENDROS LÓPEZ, Isaac. Role of Cyclooxygenase-2 on Intermittent Hypoxia-Induced Lung Tumor Malignancy in a Mouse Model of Sleep Apnea. _Scientific Reports_. 2017. Vol. 7, núm. 44693. [consulta: 20 de gener de 2026]. ISSN: 2045-2322. [Disponible a: https://hdl.handle.net/2445/121403]

Exportar metadades

JSON - METS

Compartir registre