title: 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.affiliation: NBO, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Guenhaël
authors.initials: G
authors.lastname: Sanz
authors.affiliation: Vectorologie et Thérapeutiques Anti-Cancéreuses, UMR8203, CNRS, Univ. Paris-Sud, Université Paris-Saclay, Gustave Roussy, Villejuif, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Leray
authors.affiliation: NBO, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Denise
authors.initials: D
authors.lastname: Grébert
authors.affiliation: NBO, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Sharmilee
authors.initials: S
authors.lastname: Antoine
authors.affiliation: NBO, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Acquistapace
authors.affiliation: Vectorologie et Thérapeutiques Anti-Cancéreuses, UMR8203, CNRS, Univ. Paris-Sud, Université Paris-Saclay, Gustave Roussy, Villejuif, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Muscat
authors.affiliation: GABI, AgroParisTech, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Abdelhak
authors.initials: A
authors.lastname: Boukadiri
authors.affiliation: Vectorologie et Thérapeutiques Anti-Cancéreuses, UMR8203, CNRS, Univ. Paris-Sud, Université Paris-Saclay, Gustave Roussy, Villejuif, France.
authors.forename: Lluis M
authors.initials: LM
authors.lastname: Mir
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D006801:Humans; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000819:agonists*; D009368:Neoplasm Transplantation; D045792:Norisoprenoids / Q000737:chemistry / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D018035:Receptors, Odorant / Q000819:agonists*; D015854:Up-Regulation
chemical_list: D009363:Neoplasm Proteins; D045792:Norisoprenoids; C417566:OR51E2 protein, human; D018035:Receptors, Odorant; C008157:beta-ionone; C011879:alpha-ionone
keywords: odorant ligands; olfactory receptors; prostate cancer; tumor progression