HISTOLOGY AND HISTOPATHOLOGY

From Cell Biology to Tissue Engineering

 

Estrogen-deficient osteoporosis enhances the recruitment and activity of osteoclasts by breast cancer cells

Francesca Salamanna1, Stefania Pagani1,2, Melania Maglio2, Veronica Borsari1, Gianluca Giavaresi1,2, Alberto M. Martelli3, Francesca Buontempo3 and Milena Fini1,2

1Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Rizzoli Research Innovation Technology Department, 2Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute and 3Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy

Offprint requests to: Francesca Salamanna, PhD, Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Rizzoli Research Innovation Technology Department, Rizzoli Orthopaedic Institute, Via di Barbiano, 1/10, 40136 Bologna, Italy. e-mail: francesca.salamanna@ior.it


Summary. 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. Histol Histopathol 31, 83-93 (2016)

Key words: Bone metastasis, Estrogen deficiency, Osteoporosis, Breast cancer, Osteoclasts

DOI: 10.14670/HH-11-651