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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 ?-ionone, leading to increased generation of metastases in vivo. In the present study, we show that even a relatively short exposure to ?-ionone is sufficient to promote metastasis emergence. Moreover, ?-ionone, considered an OR51E2 antagonist, in fact promotes prostate tumor growth in vivo. The combination of ?-ionone with ?-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 ?-ionone is a real agonist of OR51E2, mainly sustaining LNCaP cell growth, while ?-ionone mainly promotes cell invasiveness. So, while structurally close, ?-ionone and ?-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.

SUBMITTER: Sanz G

PROVIDER: S-EPMC5354835 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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

Sanz Guenhaël G Leray Isabelle I Grébert Denise D Antoine Sharmilee S Acquistapace Adrien A Muscat Adeline A Boukadiri Abdelhak A Mir Lluis M LM

Oncotarget 20170101 3

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 ...[more]

PMID: 28032594

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

Publications

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

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