title: An in vitro 3D bone metastasis model by using a human bone tissue culture and human sex-related cancer cells.
abstract: One of the main limitations, when studying cancer-bone metastasis, is the complex nature of the native bone environment and the lack of reliable, simple, inexpensive models that closely mimic the biological processes occurring in patients and allowing the correct translation of results. To enhance the understanding of the mechanisms underlying human bone metastases and in order to find new therapies, we developed an in vitro three-dimensional (3D) cancer-bone metastasis model by culturing human breast or prostate cancer cells with human bone tissue isolated from female and male patients, respectively. Bone tissue discarded from total hip replacement surgery was cultured in a rolling apparatus system in a normoxic or hypoxic environment. Gene expression profile, protein levels, histological, immunohistochemical and four-dimensional (4D) micro-CT analyses showed a noticeable specificity of breast and prostate cancer cells for bone colonization and ingrowth, thus highlighting the species-specific and sex-specific osteotropism and the need to widen the current knowledge on cancer-bone metastasis spread in human bone tissues. The results of this study support the application of this model in preclinical studies on bone metastases and also follow the 3R principles, the guiding principles, aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes.
authors.affiliation: Laboratory of Biocompatibility, Technological Innovation and Advanced Therapy, Rizzoli RIT, Rizzoli Orthopedic Institute, Bologna, Italy.|Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Salamanna
authors.affiliation: Laboratory of Biocompatibility, Technological Innovation and Advanced Therapy, Rizzoli RIT, Rizzoli Orthopedic Institute, Bologna, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Borsari
authors.affiliation: Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Brogini
authors.affiliation: Laboratory of Biocompatibility, Technological Innovation and Advanced Therapy, Rizzoli RIT, Rizzoli Orthopedic Institute, Bologna, Italy.|Laboratory of Tissue Engineering-Innovative Technology Platforms for Tissue Engineering, Rizzoli Orthopedic Institute, Palermo, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Giavaresi
authors.affiliation: Laboratory of Biocompatibility, Technological Innovation and Advanced Therapy, Rizzoli RIT, Rizzoli Orthopedic Institute, Bologna, Italy.
authors.forename: Annapaola
authors.initials: A
authors.lastname: Parrilli
authors.affiliation: Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy.|Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Cepollaro
authors.affiliation: I Orthopaedics and Trauma Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy.|University of Bologna, Bologna, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Cadossi
authors.affiliation: Laboratory of Biocompatibility, Technological Innovation and Advanced Therapy, Rizzoli RIT, Rizzoli Orthopedic Institute, Bologna, Italy.|Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Martini
authors.affiliation: I Orthopaedics and Trauma Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy.|University of Bologna, Bologna, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Mazzotti
authors.affiliation: Laboratory of Biocompatibility, Technological Innovation and Advanced Therapy, Rizzoli RIT, Rizzoli Orthopedic Institute, Bologna, Italy.|Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Fini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip; D014408:Biomarkers, Tumor / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018920:Coculture Techniques / Q000379:methods*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009928:Organ Specificity; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D012737:Sex Factors; D046509:Tissue Culture Techniques / Q000379:methods*; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor
keywords: 3D model; cancer-bone metastasis model; human bone tissue; human sex-related cancer cells