ecole doctorale « medicament - L`Institut de Formation Doctorale

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Proposition de sujet de thèse à l’appui d’une demande de contrat doctoral 2017-2018
Renseignements relatifs à l’Unité de Recherche :
Label et intitulé : INSERM U1151, INEM
Nom et prénom du Directeur : Nassif Xavier
Téléphone : 0172606508 Télécopie :
Courriel: xav[email protected]
Renseignements relatifs à l’Equipe :
Nom de l’Equipe d’Accueil : Equipe 4 - Physiopathologie des hormones PRL/GH : approches
transversales
Nom et prénom du responsable : Goffin Vincent
Qualité du responsable : DR2 Inserm
Téléphone : 0172606368 Télécopie : 01 72 60 64 01
Courriel : vince[email protected]
Renseignements relatifs au sujet de thèse :
Nom et prénom du Directeur de thèse (HDR) : Capiod Thierry
Qualité : CR1 Inserm
Téléphone : 0172606371 Télécopie : 01 72 60 64 01
Courriel : thierry[email protected]
Titre du sujet proposé :
(En français) Le récepteur au calcium comme acteur et biomarqueur de la progression des
cancers prostatiques avec métastases osseuses
(En anglais) Challenging the calcium sensing receptor as a promoter and biomarker of prostate
cancer progression
Département (cocher le département correspondant au sujet de thèse qui n’est pas obligatoirement le
vôtre) :
 Biologie Cellulaire et moléculaire, Physiologie et Physiopathologie
 Immunologie
 Développement Génétique Neurobiologie et Vieillissement
 Infectiologie, Microbiologie
Summary (5 lines maximum) :
We have recently shown that the calcium sensing receptor (CaSR) mediates the effect of dietary calcium
supplementation on prostate cancer progression. The aim of this project is identify the cell population
involved and to determine upstream (role of inflammation and alimentation on CaSR expression and
activity) and downstream (intracellular signaling pathways) events accounting for the deleterious effect of
calcium supplementation on prostate cancer progression.

Proposition de sujet de thèse à l’appui d’une demande de contrat doctoral 2017-2018
(L’ensemble de cette fiche ne doit pas dépasser 1 page)
Nom, prénom du directeur de l'unité de recherche : Nassif Xavier
Numéro de l'unité de recherche (et établissement de rattachement) : INSERM U1151 INEM UP5
Nom, prénom du responsable de l'équipe d'accueil (EAD) : Goffin Vincent
Nom, prénom du directeur de thèse : Capiod Thierry
Titre du sujet de thèse proposé :
(en anglais) Challenging the calcium sensing receptor as a promoter and biomarker of prostate
cancer progression
Citer 5 mots clés : prostate, inflammation, calcium signaling, nutrition, bone metastasis
Candidat pressenti :  OUI  NON
Contenu scientifique du programme de la thèse (en anglais)
We have recently shown that calcium supplementation promotes prostate cancer progression through calcium
sensing receptors (CaSR) overexpression in vivo and in vitro (Bernichtein et al, 2017). These CaSR are able to
detect and convert increases in calcemia into intracellular responses through coupling to specific G protein
subunits determining cell fate eventually. The aim of this project is to determine which prostate cell population is
targeted, what upstream and downstream events are involved to promote the deleterious effect of high calcium
diets during cancer progression, and how this relates to bone metastasis. This will be addressed using 7 well
characterized human prostate cancer cell lines (ATCC) differing among others by their androgen-sensitivity.
Cancer and inflammation are intimately related and CaSR expression is controlled by cytokines. However,
inflammation and calcium supplementation does not always trigger cancer. Our working hypothesis is to identify the
targeted prostate cell population in human tissue samples as well as the nature of the cytokine and the associated
intracellular signaling pathways triggering CaSR expression increase in cell lines. In the same extent, CaSR
stimulation does not trigger cell proliferation in all human prostate cell lines. Therefore, studying the coupling of
CaSR to specific cell functions and cell fate is essential to understand these deleterious effects of calcium
supplementation. Moreover, L-amino acids (present in red meat) are also CaSR allosteric regulators potentiating
calcium responses. Investigating the combined effect of inflammation and L-amino acids on the sensitivity and
effectiveness of calcium-induced responses is essential and should provide solid data to establish active nutritional
surveillance in patients with prostate cancer. Finally, the most aggressive forms of prostate cancer are no longer
sensitive to androgen deprivation and the relationship between CaSR and androgen receptor expression will be
investigated in prostate cancer cell lines and tissues.
CaSR expression is elevated in bone metastasis in patients with prostate cancer. The high calcium environment in
bone is likely to amplify the ability of CaSR expressing prostate cancer cells to invade and proliferate and we shall
study the mechanisms by which metastasis can develop.
Indiquez les cinq meilleures publications récentes de l’équipe :
- Laget S, Broncy L, Hormigos K, Dhingra DM, BenMohamed F, Capiod T, Osteras M, Farinelli L, Jackson S,
Paterlini-Bréchot P. Technical Insights into Highly Sensitive Isolation and Molecular Characterization of Fixed and
Live Circulating Tumor Cells for Early Detection of Tumor Invasion. PLoS One. 2017 Jan 6;12(1):e0169427
- Bernichtein S, Pigat N, Barry Delongchamps N, Boutillon F, Verkarre V, Camparo P, Reyes-Gomez E, Méjean A,
Oudard SM, Lepicard EM, Viltard M, Souberbielle JC, Friedlander G, *Capiod T, *Goffin V. Vitamin D3 Prevents
Calcium-Induced Progression of Early-Stage Prostate Tumors by Counteracting TRPC6 and Calcium Sensing
Receptor Upregulation. Cancer Res. 2017 Jan 15;77(2):355-365
- Orhon I, Dupont N, Zaidan M, Boitez V, Burtin M, Schmitt A, Capiod T, Viau A, Beau I, Kuehn EW, Friedlander G,
Terzi F, Codogno P. Primary-cilium-dependent autophagy controls epithelial cell volume in response to fluid flow.
Nat Cell Biol. 2016 Jun;18(6):657-67
- Capiod T. Extracellular Calcium Has Multiple Targets to Control Cell Proliferation. Adv Exp Med Biol.
2016;898:133-56
- *Bernichtein S, *Pigat N, *Capiod T, Boutillon F, Verkarre V, Camparo P, Viltard M, Méjean A, Oudard S,
Souberbielle JC, Friedlander G, Goffin V. High milk consumption does not affect prostate tumor progression in two
mouse models of benign and neoplastic lesions. PLoS One. 2015 May 4;10(5):e0125423