Promotion of cancer cell invasiveness and metastasis emergence caused by olfactory receptor stimulation

Guenhaël Sanz (1, 2) , Isabelle Leray (3, 4) , Aurélie Dewaele (1, 2) , Julien Sobilo (5) , Stéphanie Lerondel (6) , Stephan Bouet (7, 8) , Denise Grebert (1, 9) , Regine Monnerie (1, 9) , Edith Pajot (1, 9) , Lluis Maria Mir (3, 4)

1 NBO - Neurobiologie de l'olfaction
2 IFR 144 Neuro-Sud
3 UMR 8203 - Vectorologie et thérapeutiques anti-cancéreuses [Villejuif]
4 UP11 - Université Paris-Sud - Paris 11
5 Centre d'imagerie du Petit Animal
6 Cente d'imagerie du Petit Animal
7 GABI - Génétique Animale et Biologie Intégrative
8 LREG - Laboratoire de radiobiologie et d'étude du génome
9 IFR 144 - Institut Fédératif de Recherche 144 (NeuroSud Paris)

Olfactory receptors (ORs) are expressed in the olfactory epithelium, where they detect odorants, but also in other tissues with additional functions. Some ORs are even overexpressed in tumor cells. In this study, we identified ORs expressed in enterochromaffin tumor cells by RT-PCR, showing that single cells can co-express several ORs. Some of the receptors identified were already reported in other tumors, but they are orphan (without known ligand), as it is the case for most of the hundreds of human ORs. Thus, genes coding for human ORs with known ligands were transfected into these cells, expressing functional heterologous ORs. The in vitro stimulation of these cells by the corresponding OR odorant agonists promoted cell invasion of collagen gels. Using LNCaP prostate cancer cells, the stimulation of the PSGR (Prostate Specific G protein-coupled Receptor), an endogenously overexpressed OR, by beta-ionone, its odorant agonist, resulted in the same phenotypic change. We also showed the involvement of a PI3 kinase gamma dependent signaling pathway in this promotion of tumor cell invasiveness triggered by OR stimulation. Finally, after subcutaneous inoculation of LNCaP cells into NSG immunodeficient mice, the in vivo stimulation of these cells by the PSGR agonist beta-ionone significantly enhanced metastasis emergence and spreading.

Domaines: Sciences du Vivant [q-bio]

Guenhaël Sanz, Isabelle Leray, Aurélie Dewaele, Julien Sobilo, Stéphanie Lerondel, et al.. Promotion of cancer cell invasiveness and metastasis emergence caused by olfactory receptor stimulation. PLoS ONE, 2014, 9 (1), ⟨10.1371/journal.pone.0085110⟩. ⟨hal-01189887⟩