title: Estrogen-deficient osteoporosis enhances the recruitment and activity of osteoclasts by breast cancer cells.
abstract: To reduce the burden of bone metastases, the pathophysiology of the metastatic niche should be elucidated and targeted. The aim of the present study was to assess the effect of tumor cells on osteoclast (OC) recruitment and activity in the presence of altered bone remodelling. Peripheral blood mononuclear cells (PBMC) were isolated from healthy and ovariectomized (OVX) rats and co-cultured with MRMT-1 rat breast carcinoma cells or with their conditioned medium for 1 and 2 weeks. Alamar Blue viability test, synthesis of cathepsin K, transforming growth factor-beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), metalloproteinase (MMP)-7, MMP-9, FITC-conjugate phalloidin staining and tartrate-resistant acid phosphatase (TRAP) staining were evaluated. The results indicate that breast carcinoma cells induced different responses in PBMC derived from rats affected by estrogen deficiency osteoporosis (OP) in comparison with healthy ones, with a significant increase in proliferation rate, OC differentiation, synthesis of TNF-α, MMP-7 and MMP-9. The data support the "proof of concept" that OP due to estrogen deficiency might offer a receptive site for cancer cells to form bone metastases.
authors.affiliation: Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Rizzoli Research Innovation Technology Department, Bologna, Italy. francesca.salamanna@ior.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Salamanna
authors.affiliation: Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Rizzoli Research Innovation Technology Department, and Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pagani
authors.affiliation: Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Melania
authors.initials: M
authors.lastname: Maglio
authors.affiliation: Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Rizzoli Research Innovation Technology Department, Bologna, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Borsari
authors.affiliation: Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Rizzoli Research Innovation Technology Department, and Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Giavaresi
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Martelli
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Buontempo
authors.affiliation: Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Rizzoli Research Innovation Technology Department, and Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Fini
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D009000:Monocytes / Q000473:pathology*; D010010:Osteoclasts / Q000473:pathology*; D010024:Osteoporosis / Q000473:pathology*; D010052:Ovariectomy; D051381:Rats
chemical_list: D014408:Biomarkers, Tumor; D004967:Estrogens