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标题：Iloprost requires the Frizzled-9 receptor to prevent lung cancer
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作者：Kayla Sompel ; Lori D. Dwyer-Nield ; Alex J. Smith 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：6
页码：1-19
DOI：10.1016/j.isci.2022.104442
语种：English
出版社：Elsevier
摘要：SummaryPrevention 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 andin vitro, which requires the transmembrane receptor Frizzled9(FZD9). We hypothesized aFzd9−/−mouse would not be protected by iloprost in a lung cancer model.Fzd9−/−mice were treated with inhaled iloprost in a urethane model of lung adenoma. We found thatFzd9−/−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 FZD9in vivofor 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.Graphical abstractDisplay OmittedHighlights•Loss of Frizzled 9 reduces the lung cancer chemopreventive effect of iloprost in mice•Lung cancer prevention by prostacyclin synthase in mice does not require Frizzled 9•Activation of iloprost downstream targets is reduced with loss of Frizzled 9Biological sciences; Biochemistry; Cancer