title: Promotion of cancer cell invasiveness and metastasis emergence caused by olfactory receptor stimulation.
abstract: 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 β-ionone, its odorant agonist, resulted in the same phenotypic change. We also showed the involvement of a PI3 kinase γ 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 β-ionone significantly enhanced metastasis emergence and spreading.
authors.affiliation: INRA, UR1197 Neurobiologie de l'Olfaction et Modélisation en Imagerie, Jouy-en-Josas, France ; IFR 144 NeuroSud Paris, Gif-sur-Yvette, France.
authors.forename: Guenhaël
authors.initials: G
authors.lastname: Sanz
authors.affiliation: CNRS, UMR8203 Vectorologie et thérapeutiques anti-cancéreuses, Institut Gustave-Roussy, Villejuif, France ; Univ. Paris-Sud, UMR8203, Orsay, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Leray
authors.affiliation: INRA, UR1197 Neurobiologie de l'Olfaction et Modélisation en Imagerie, Jouy-en-Josas, France ; IFR 144 NeuroSud Paris, Gif-sur-Yvette, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Dewaele
authors.affiliation: CNRS-TAAM, UPS44, Centre d'Imagerie du Petit Animal, Orléans, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Sobilo
authors.affiliation: CNRS-TAAM, UPS44, Centre d'Imagerie du Petit Animal, Orléans, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lerondel
authors.affiliation: INRA, UMR 1313, Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France ; CEA, DSV, IRCM, SREIT, Laboratoire de Radiobiologie et Etude du Génome, Jouy-en-Josas, France ; AgroParisTech, UMR 1313, Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France.
authors.forename: Stéphan
authors.initials: S
authors.lastname: Bouet
authors.affiliation: INRA, UR1197 Neurobiologie de l'Olfaction et Modélisation en Imagerie, Jouy-en-Josas, France ; IFR 144 NeuroSud Paris, Gif-sur-Yvette, France.
authors.forename: Denise
authors.initials: D
authors.lastname: Grébert
authors.affiliation: INRA, UR1197 Neurobiologie de l'Olfaction et Modélisation en Imagerie, Jouy-en-Josas, France ; IFR 144 NeuroSud Paris, Gif-sur-Yvette, France.
authors.forename: Régine
authors.initials: R
authors.lastname: Monnerie
authors.affiliation: INRA, UR1197 Neurobiologie de l'Olfaction et Modélisation en Imagerie, Jouy-en-Josas, France ; IFR 144 NeuroSud Paris, Gif-sur-Yvette, France.
authors.forename: Edith
authors.initials: E
authors.lastname: Pajot-Augy
authors.affiliation: CNRS, UMR8203 Vectorologie et thérapeutiques anti-cancéreuses, Institut Gustave-Roussy, Villejuif, France ; Univ. Paris-Sud, UMR8203, Orsay, France.
authors.forename: Lluis M
authors.initials: LM
authors.lastname: Mir
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D003094:Collagen / Q000737:chemistry; D004759:Enterochromaffin Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005782:Gels; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D045792:Norisoprenoids / Q000009:adverse effects*; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D018035:Receptors, Odorant / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D005782:Gels; D009363:Neoplasm Proteins; D045792:Norisoprenoids; C417566:OR51E2 protein, human; D021122:Protein Subunits; D018035:Receptors, Odorant; D003094:Collagen; C008157:beta-ionone; D019869:Phosphatidylinositol 3-Kinases; D002118:Calcium