Variability of the paracrine-induced osteoclastogenesis by human breast cancer cell lines

Breast cancer frequently metastasizes to the bone, often leading to the formation of osteolytic lesions. This work compares the paracrine-induced osteoclastogenesis mediated by four human breast cancer cell lines, the estrogen-receptor positive T47D and MCF-7 and the estrogen-negative SK-BR-3 and Hs-578T cell lines. Human osteoclast precursor cells were cultured in the presence of conditioned media from the breast cancer cell lines (10% and 20%), collected at different culture periods (48 h, 7 days, and 14 days). Cultures performed in the absence or the presence of M-CSF and RANKL served as negative and positive control, respectively. Results showed that the cell lines differentially expressed several osteoclastogenic genes. All cell lines exhibited a significant osteoclastogenic potential, evidenced by a high TRAP activity and number of osteoclastic cells, expression of several osteoclast-related genes, and, particularly, a high calcium phosphate resorption activity. Differences among the osteoclastogenic potential of the cell lines were noted. T47D and MCF-7 cell lines displayed the highest and the lowest osteoclastogenic response, respectively. Despite the variability observed, MEK and NF-κB signaling pathways, and, at a lesser extent, PGE2 production, seemed to have a central role on the observed osteoclastogenic response. In conclusion, the tested breast cancer cell lines exhibited a high osteoclastogenic potential, although with some variability on the cell response profile, a factor to be considered in the development of new therapeutic approaches for breast cancer-induced bone metastasis.