No curative treatment options exist once breast cancer metastasizes to bone. This is due, in part, to an incomplete understanding of how osteolytic cancers interact with bone. Presented here is a novel approach to study the interactions between triple negative breast cancer cells and osteoblasts within a 3D collagenous environment. More specifically, a dense collagen hydrogel was employed to model interactions between MDA-MB-231 breast cancer cells and MC3T3-E1 pre-osteoblasts. Co-cultures with these two cell types, or MDA-MB-231-derived conditioned medium applied to MC3T3-E1 cells, were established in the context of plastically compressed dense collagen gel matrices. Importantly, breast cancer-derived conditioned medium or the establishment of breast cancer/osteoblast co-cultures did not negatively influence MC3T3-E1 cell viability. The inclusion of either conditioned medium or the presence of MDA-MB-231 cells resulted in impaired MC3T3-E1 differentiation into osteoblasts, which coincided with reduced osteoblast-mediated mineralization. The results presented here demonstrate that dense collagen gels provide a model environment to examine the effect of osteolytic breast cancer cells on osteoblast differentiation and subsequent mineralization of the collagen scaffold.
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