par Iuliani, Michele;Pantano, Francesco;Buttigliero, Consuelo;Fioramonti, Marco ;Bertaglia, Valentina;Vincenzi, Bruno;Zoccoli, Alice;Ribelli, Giulia;Tucci, Marcello;Vignani, Francesca;Berruti, Alfredo;Scagliotti, Giorgio Vittorio;Tonini, Giuseppe;Santini, Daniele
Référence Oncotarget, 6, 14, page (12520-12528)
Publication Publié, 2015-05
Référence Oncotarget, 6, 14, page (12520-12528)
Publication Publié, 2015-05
Article révisé par les pairs
Résumé : | Abiraterone acetate (ABI) is associated not only with a significant survival advantage in both chemotherapy-naive and -treated patients with metastatic castration-resistant prostate cancer (mCRPC), but also with a delay in time to development of Skeletal Related Events and in radiological skeletal progression. These bone benefits may be related to a direct effect on prostate cancer cells in bone or to a specific mechanism directed to bone microenvironment. To test this hypothesis we designed an in vitro study aimed to evaluate a potential direct effect of ABI on human primary osteoclasts/osteoblasts (OCLs/OBLs). We also assessed changes in bone turnover markers, serum carboxy-terminal collagen crosslinks (CTX) and alkaline phosphatase (ALP), in 49 mCRPC patients treated with ABI.Our results showed that non-cytotoxic doses of ABI have a statistically significant inhibitory effect on OCL differentiation and activity inducing a down-modulation of OCL marker genes TRAP, cathepsin K and metalloproteinase-9. Furthermore ABI promoted OBL differentiation and bone matrix deposition up-regulating OBL specific genes, ALP and osteocalcin. Finally, we observed a significant decrease of serum CTX values and an increase of ALP in ABI-treated patients.These findings suggest a novel biological mechanism of action of ABI consisting in a direct bone anabolic and anti-resorptive activity. |