TY - JOUR
T1 - Estrogen-deficient osteoporosis enhances the recruitment and activity of osteoclasts by breast cancer cells
AU - Salamanna, Francesca
AU - Pagani, Stefania
AU - Maglio, Melania
AU - Borsari, Veronica
AU - Giavaresi, Gianluca
AU - Martelli, Alberto M.
AU - Buontempo, Francesca
AU - Fini, Milena
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
KW - Bone metastasis
KW - Breast cancer
KW - Estrogen deficiency
KW - Osteoclasts
KW - Osteoporosis
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U2 - 10.14670/HH-11-651
DO - 10.14670/HH-11-651
M3 - Article
C2 - 26254457
AN - SCOPUS:84949058429
VL - 31
SP - 83
EP - 93
JO - Histology and Histopathology
JF - Histology and Histopathology
SN - 0213-3911
IS - 1
ER -