title: Biological and clinical effects of abiraterone on anti-resorptive and anabolic activity in bone microenvironment.
abstract: 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.
authors.affiliation: Translational Oncology Laboratory, Medical Oncology, University Campus Bio-Medico of Rome, Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Iuliani
authors.affiliation: Translational Oncology Laboratory, Medical Oncology, University Campus Bio-Medico of Rome, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pantano
authors.affiliation: Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Turin, Italy.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Buttigliero
authors.affiliation: Translational Oncology Laboratory, Medical Oncology, University Campus Bio-Medico of Rome, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Fioramonti
authors.affiliation: Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Turin, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bertaglia
authors.affiliation: Translational Oncology Laboratory, Medical Oncology, University Campus Bio-Medico of Rome, Rome, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.affiliation: Translational Oncology Laboratory, Medical Oncology, University Campus Bio-Medico of Rome, Rome, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Zoccoli
authors.affiliation: Translational Oncology Laboratory, Medical Oncology, University Campus Bio-Medico of Rome, Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ribelli
authors.affiliation: Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Turin, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tucci
authors.affiliation: Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Turin, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vignani
authors.affiliation: U.O. Oncologia Medica, Ospedali Civili di Brescia, Brescia, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berruti
authors.affiliation: Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Turin, Italy.
authors.forename: Giorgio Vittorio
authors.initials: GV
authors.lastname: Scagliotti
authors.affiliation: Translational Oncology Laboratory, Medical Oncology, University Campus Bio-Medico of Rome, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
authors.affiliation: Translational Oncology Laboratory, Medical Oncology, University Campus Bio-Medico of Rome, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000736:Androstenes / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D024042:Collagen Type I / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D010006:Osteoblasts / Q000187:drug effects*; D010010:Osteoclasts / Q000187:drug effects*; D010455:Peptides / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D000736:Androstenes; D000970:Antineoplastic Agents; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000469:Alkaline Phosphatase; C089740:abiraterone
keywords: abiraterone acetate; bone marker; osteoblast; osteoclast