Structurally related odorant ligands of the olfactory receptor OR51E2 differentially promote metastasis emergence and tumor growth.
|
| Abstract |
Olfactory receptors are G protein-coupled receptors. Some of them are expressed in tumor cells, such as the OR51E2 receptor overexpressed in LNCaP prostate cancer cells. It is considered a prostate tumor marker. We previously demonstrated that this receptor is able to promote LNCaP cell invasiveness in vitro upon stimulation with its odorant agonist β-ionone, leading to increased generation of metastases in vivo. In the present study, we show that even a relatively short exposure to β-ionone is sufficient to promote metastasis emergence. Moreover, α-ionone, considered an OR51E2 antagonist, in fact promotes prostate tumor growth in vivo. The combination of α-ionone with β-ionone triggers a higher increase in the total tumor burden than each molecule alone. To support the in vivo results, we demonstrate in vitro that α-ionone is a real agonist of OR51E2, mainly sustaining LNCaP cell growth, while β-ionone mainly promotes cell invasiveness. So, while structurally close, α-ionone and β-ionone appear to induce different cellular effects, both leading to increased tumor aggressiveness. This behaviour could be explained by a different coupling to downstream effectors, as it has been reported for the so-called biased ligands of other G protein-coupled receptors.
|
|---|---|
| Authors | Guenhaël Sanz, Isabelle Leray, Denise Grébert, Sharmilee Antoine, Adrien Acquistapace, Adeline Muscat, Abdelhak Boukadiri, Lluis M Mir |
| Journal | Oncotarget (Oncotarget) Vol. 8 Issue 3 Pg. 4330-4341 (Jan 17 2017) ISSN: 1949-2553 [Electronic] United States |
| PMID | 28032594 (Publication Type: Journal Article) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!