Structurally related odorant ligands of the olfactory receptor OR51E2 differentially promote metastasis emergence and tumor growth
Metrics: PDF 963 views | HTML 1850 views | ?
Guenhaël Sanz1, Isabelle Leray2, Denise Grébert1, Sharmilee Antoine1, Adrien Acquistapace1, Adeline Muscat2, Abdelhak Boukadiri3, Lluis M. Mir2
1NBO, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France
2Vectorologie et thérapeutiques anti-cancéreuses, UMR8203, CNRS, Univ. Paris-Sud, Université Paris-Saclay, Gustave Roussy, Villejuif, France
3GABI, AgroParisTech, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France
Guenhaël Sanz, email: firstname.lastname@example.org
Lluis M. Mir, email: Luis.MIR@cnrs.fr
Keywords: olfactory receptors, odorant ligands, tumor progression, prostate cancer
Received: September 06, 2016 Accepted: November 30, 2016 Published: December 09, 2016
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.