Bone metastases represent a major challenge in the treatment of breast cancer, but the complex interactions involved have hampered the development of robust in vitro models. The aim of this work is to investigate the osteoclastogenic potential of the osteotropic, human breast cancer cell line SCP2, evaluating its modulation by bone marrow-derived mesenchymal stromal cells (MSC) in presence or absence of the EGFR-blocking compound gefitinib. While conditioned medium (CM) from MSC did not induce osteoclastogenesis in human peripheral blood mononuclear cells (PBMC) we showed that CM from SCP2 and from SCP2-MSC cocultures increased the osteoclastogenesis of PBMC, as evidenced both by functional and molecular assays. Furthermore, the effect of CM from SCP2 treated with gefitinib on osteoclast differentiation was reduced. Moreover, although we couldnt demonstrate a straightforward effect of the EGFR pathway in the osteoclastogenic activity of SCP2, either the treatment of SCP2 with gefitinib or coculture with MSC comparably altered the expression of the bone-related marker RANK. In conclusion, we have developed an in vitro human model of coculture of cancer cells, MSCs and osteoclasts, reporting the modulation of the osteoclastogenic potential of SCP2, applying it also in the context of advanced breast cancer drug testing.
Disclosure: The authors declared no competing interests.