CaV3.2 T-type calcium channels are involved in calcium-dependent secretion of neuroendocrine prostate cancer cells.
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.
Gackière
Florian
F
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.
Bidaux
Gabriel
G
Delcourt
Philippe
P
Van Coppenolle
Fabien
F
Katsogiannou
Maria
M
Dewailly
Etienne
E
Bavencoffe
Alexis
A
Van Chuoï-Mariot
Myriam Tran
MT
Mauroy
Brigitte
B
Prevarskaya
Natalia
N
Mariot
Pascal
P
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
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