Oncotarget

Research Papers:

Structurally related odorant ligands of the olfactory receptor OR51E2 differentially promote metastasis emergence and tumor growth

Guenhaël Sanz, Isabelle Leray, Denise Grébert, Sharmilee Antoine, Adrien Acquistapace, Adeline Muscat, Abdelhak Boukadiri and Lluis M. Mir _

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Oncotarget. 2017; 8:4330-4341. https://doi.org/10.18632/oncotarget.13836

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Abstract

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

Correspondence to:

Guenhaël Sanz, email: guenhael.sanz@inra.fr

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

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.


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