title: Role of cationic channel TRPV2 in promoting prostate cancer migration and progression to androgen resistance.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U-800, Equipe labellisée par la Ligue Nationale contre le cancer, France.
authors.forename: Michaël
authors.initials: M
authors.lastname: Monet
authors.forename: V'yacheslav
authors.initials: V
authors.lastname: Lehen'kyi
authors.forename: Florian
authors.initials: F
authors.lastname: Gackiere
authors.forename: Virginie
authors.initials: V
authors.lastname: Firlej
authors.forename: Matthieu
authors.initials: M
authors.lastname: Vandenberghe
authors.forename: Morad
authors.initials: M
authors.lastname: Roudbaraki
authors.forename: Dimitra
authors.initials: D
authors.lastname: Gkika
authors.forename: Albin
authors.initials: A
authors.lastname: Pourtier
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bidaux
authors.forename: Christian
authors.initials: C
authors.lastname: Slomianny
authors.forename: Philippe
authors.initials: P
authors.lastname: Delcourt
authors.forename: François
authors.initials: F
authors.lastname: Rassendren
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bergerat
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Ceraline
authors.forename: Florence
authors.initials: F
authors.lastname: Cabon
authors.forename: Sandrine
authors.initials: S
authors.lastname: Humez
authors.forename: Natalia
authors.initials: N
authors.lastname: Prevarskaya
mesh_terms: D000728:Androgens / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050916:TRPV Cation Channels / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000728:Androgens; D050916:TRPV Cation Channels; C400769:TRPV2 protein, human; D049452:Green Fluorescent Proteins