| First Author | Sompel K | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 6 | Pages | 104442 |
| PubMed ID | 35707728 | Mgi Jnum | J:325978 |
| Mgi Id | MGI:7293895 | Doi | 10.1016/j.isci.2022.104442 |
| Citation | Sompel K, et al. (2022) Iloprost requires the Frizzled-9 receptor to prevent lung cancer. iScience 25(6):104442 |
| abstractText | 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 Frizzled9 (FZD9). 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 FZD9 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. |
