Iloprost requires the Frizzled-9 receptor to prevent lung cancer.

Autor:	Sompel K; Division of Pulmonary Sciences and Critical Care Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Dwyer-Nield LD; Skaggs School of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Smith AJ; Division of Pulmonary Sciences and Critical Care Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Elango A; Division of Pulmonary Sciences and Critical Care Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Backos DS; Skaggs School of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Zhang B; National Jewish Health, Denver, CO, USA., Gross J; National Jewish Health, Denver, CO, USA., Ternyak K; National Jewish Health, Denver, CO, USA., Matsuda JL; National Jewish Health, Denver, CO, USA., Kopf K; National Jewish Health, Denver, CO, USA., Keith RL; Division of Pulmonary Sciences and Critical Care Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Rocky Mountain Regional VA Medical Center, Aurora, CO, USA., Tennis MA; Division of Pulmonary Sciences and Critical Care Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2022 May 23; Vol. 25 (6), pp. 104442. Date of Electronic Publication: 2022 May 23 (Print Publication: 2022).
DOI:	10.1016/j.isci.2022.104442
Abstrakt:	Prevention of premalignant lesion progression is a promising approach to reducing lung cancer burden in high-risk populations. Substantial preclinical and clinical evidence has demonstrated efficacy of the prostacyclin analogue iloprost for lung cancer chemoprevention. Iloprost activates peroxisome proliferator-activated receptor gamma (PPARG) to initiate chemopreventive signaling and in vitro , which requires the transmembrane receptor Frizzled 9 (FZD 9 ). We hypothesized a Fzd 9 -/- mouse would not be protected by iloprost in a lung cancer model. Fzd 9 -/- mice were treated with inhaled iloprost in a urethane model of lung adenoma. We found that Fzd 9 -/- mice treated with iloprost were not protected from adenoma development compared to wild-type mice nor did they demonstrate increased activation of iloprost signaling pathways. Our results established that iloprost requires FZD 9 in vivo for lung cancer chemoprevention. This work represents a critical advancement in defining iloprost's chemopreventive mechanisms and identifies a potential response marker for future clinical trials. Competing Interests: The authors declare no competing interests. (© 2022 The Author(s).)
Databáze:	MEDLINE
Externí odkaz: