Institut National de la Santé et de la Recherche Médicale, U-800, Equipe labellisée par la Ligue Nationale contre le cancer; Université des Sciences et Technologies de Lille, Villeneuve d'Ascq, France.

Centre National de la Recherche Scientifique, University Paris-Sud, FRE2944, Epigenetics and Cancer, Institut André Lwoff, Villejuif, France; UMR 8161 Institut de Biologie de Lille Centre National de la Recherche Scientifique/Université Université Lille 1 et 2/Institut Pasteur de Lille, Lille, France; Département de Pharmacologie, Institut de Génomique Fonctionnelle, Centre National de la Recherche Scientifique UMR 5203, Institut National de la Santé et de la Recherche Médicale U661, Université Montpellier I, Université Montpellier II, Montpellier Cedex, France; Département d'Onco-Hématologie, Hôpitaux Universitaires de Strasbourg; Unité Physiopathologie et Médecine Translationnelle, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; and Université d'Artois, Faculté des Sciences Jean Perrin, Lens, France.

Castration resistance in prostate cancer (PCa) constitutes an advanced, aggressive disease with poor prognosis, associated with uncontrolled cell proliferation, resistance to apoptosis, and enhanced invasive potential. The molecular mechanisms involved in the transition of PCa to castration resistance are obscure. Here, we report that the nonselective cationic channel transient receptor potential vanilloid 2 (TRPV2) is a distinctive feature of castration-resistant PCa. TRPV2 transcript levels were higher in patients with metastatic cancer (stage M1) compared with primary solid tumors (stages T2a and T2b). Previous studies of the TRPV2 channel indicated that it is primarily involved in cancer cell migration and not in cell growth. Introducing TRPV2 into androgen-dependent LNCaP cells enhanced cell migration along with expression of invasion markers matrix metalloproteinase (MMP) 9 and cathepsin B. Consistent with the likelihood that TRPV2 may affect cancer cell aggressiveness by influencing basal intracellular calcium levels, small interfering RNA-mediated silencing of TRPV2 reduced the growth and invasive properties of PC3 prostate tumors established in nude mice xenografts, and diminished expression of invasive enzymes MMP2, MMP9, and cathepsin B. Our findings establish a role for TRPV2 in PCa progression to the aggressive castration-resistant stage, prompting evaluation of TRPV2 as a potential prognostic marker and therapeutic target in the setting of advanced PCa.

Written by:
Monet M, Lehen'kyi V, Gackiere F, Firlej V, Vandenberghe M, Roudbaraki M, Gkika D, Pourtier A, Bidaux G, Slomianny C, Delcourt P, Rassendren F, Bergerat JP, Ceraline J, Cabon F, Humez S, Prevarskaya N. Are you the author?

Reference:
Cancer Res. 2010 Feb 1;70(3):1225-1235.
doi:10.1158/0008-5472.CAN-09-2205

PubMed Abstract
PMID:20103638

UroToday.com Prostate Cancer Section

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