title: CaV3.2 T-type calcium channels are involved in calcium-dependent secretion of neuroendocrine prostate cancer cells.
abstract: Because prostate cancer is, in its early stages, an androgen-dependent pathology, treatments aiming at decreasing testosterone plasma concentration have been developed for many years now. However, a significant proportion of patients suffer a relapse after a few years of hormone therapy. The androgen-independent stage of prostate cancer has been shown to be associated with the development of neuroendocrine differentiation. We previously demonstrated that neuroendocrine prostate cancer cells derived from LNCaP cells overexpress CaV3.2 T-type voltage-dependent calcium channels. We demonstrate here using prostatic acid phosphatase as a marker of prostate secretion and FM1-43 fluorescence imaging of membrane trafficking that neuroendocrine differentiation is associated with an increase in calcium-dependent secretion which critically relies on CaV3.2 T-type calcium channel activity. In addition, we show that these channels are expressed by neuroendocrine cells in prostate cancer tissues obtained from patients after surgery. We propose that CaV3.2 T-type calcium channel up-regulation may account for the alteration of secretion during prostate cancer development and that these channels, by promoting the secretion of potential mitogenic factors, could participate in the progression of the disease toward an androgen-independent stage.
authors.affiliation: INSERM U800, Laboratoire de Physiologie Cellulaire, Equipe Labellisée par la Ligue contre le Cancer and Université des Sciences et Technologies de Lille, Villeneuve d'Ascq, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Gackière
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bidaux
authors.forename: Philippe
authors.initials: P
authors.lastname: Delcourt
authors.forename: Fabien
authors.initials: F
authors.lastname: Van Coppenolle
authors.forename: Maria
authors.initials: M
authors.lastname: Katsogiannou
authors.forename: Etienne
authors.initials: E
authors.lastname: Dewailly
authors.forename: Alexis
authors.initials: A
authors.lastname: Bavencoffe
authors.forename: Myriam Tran
authors.initials: MT
authors.lastname: Van Chuoï-Mariot
authors.forename: Brigitte
authors.initials: B
authors.lastname: Mauroy
authors.forename: Natalia
authors.initials: N
authors.lastname: Prevarskaya
authors.forename: Pascal
authors.initials: P
authors.lastname: Mariot
mesh_terms: D000135:Acid Phosphatase; D000728:Androgens / Q000097:blood; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D006133:Growth Substances / Q000378:metabolism*; D020249:Hormone Replacement Therapy; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D015854:Up-Regulation
chemical_list: D000728:Androgens; D014408:Biomarkers, Tumor; C479952:CACNA1H protein, human; D020747:Calcium Channels, T-Type; D006133:Growth Substances; D013739:Testosterone; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases; D002118:Calcium