Calcium release from hydroxyapatite particles influences breast cancer cell osteomimicry and osteolytic behaviors in bone metastases

Bone metastases account for the majority of deaths from breast cancer (BCa) and produce painful osteolytic lesions through osteoclast hyperactivation. However, the reciprocal interaction between BCa cells and the metastatic bone niche in regulating the osteolytic process remains largely unknown. Therefore, we examined the effect of bone microenvironmental cues on the acquisition of osteomimetic features (expression of bone-cell markers to bypass immune monitoring) by MDA-MB-231 triple-negative BCa cells. Four different hydroxyapatite (HA) particles in the micron size range (3-25<i>µ</i>m) with varying physiochemical characteristics were combined with type I collagen matrix. This produced composites to emulate the secondary bone metastasis niche at the bone marrow-cortical bone interface we termed the 'bone bioengineered interfaces' (BBIs). We showed that passive calcium dissolution from HA crystals in the BBIs is a critical bio-determinant related to MDA-MB-231 cells' osteomimicry and osteoclastogenesis of THP-1 monocytic cells in bone metastasis. These findings provide novel insights into the mechanisms of the reciprocal interaction between BCa cells and the metastatic bone microenvironment and pave the way for the potential use of more effective and environmentally friendly approaches for personalised medicine platforms and tailored therapeutic strategies.