Aquaretic inhibits renal cancer proliferation: Role of vasopressin receptor-2 (V2-R).
Vasopressin (AVP) is a hormone with antidiuretic properties that is also involved in cellular proliferation of breast, pulmonary, and pancreatic neoplasias, attributable to the interaction with specific receptors, among which is the V2-R. Using a culture model of CAKI-2 and A498 cancer cells, our study aimed to verify if renal carcinoma cells also express V2-R and whether receptor activation modulates their proliferation. Immunofluorescence and RT-PCR showed that both CAKI-2 and A498 cells effectively synthesize and express the V2-R. Administration of the vasopressin analogue DDAVP induced an evident growth in both CAKI-2 and A498 cell lines. However, this proliferative effect was completely avoided by the preventive addition of the V2-R antagonist SR121463B (satavaptan). Our study shows for the first time that renal cancer may effectively synthesize and express the V2-R. Furthermore, AVP exerts in vitro a proliferative effect by acting on this receptor, as the selective V2-R blockage is able to completely prevent the cellular growth. A validation of these findings with in vivo models is required to ascertain if the eventual presence of V2-R could influence the aggressiveness of human renal neoplasias. From this point of view, a new, interesting therapeutical application of V2-R antagonists in the treatment of renal cancer could also be proposed, similar to that successfully described in the treatment of autosomal polycystic kidney disease (ADPKD).
Bolignano
Davide
D
Department of Internal Medicine, University of Messina, Messina, Italy.
Medici
Maria Antonietta
MA
Coppolino
Giuseppe
G
Sciortino
Maria Teresa
MT
Merlo
Francesca Marino
FM
Campo
Susanna
S
Donato
Valentina
V
Venuti
Assunta
A
Sturiale
Alessio
A
Zaccaria
Daniela
D
Buemi
Antoine
A
Lacquaniti
Antonio
A
Buemi
Michele
M
D000368:Aged; D050034:Antidiuretic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism*; D008297:Male; D017483:Receptors, Vasopressin / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014667:Vasopressins / Q000378:metabolism*
D050034:Antidiuretic Agents; D017483:Receptors, Vasopressin; D014667:Vasopressins; D003894:Deamino Arginine Vasopressin