Biomineralized scaffolds as an in vitro platform for studying metastatic bone disease

Osteolytic bone metastasis is a devastating complication of breast cancer that causes severe reduction in quality of life and is frequently the cause of death in breast cancer patients. Biomimetic model systems are invaluable tools for studying how microenvironmental conditions control tumorigenesis and metastasis in vivo. Biomaterial design principles and tissue engineering strategies were employed to create three-dimensional biomineralized polymeric scaffolds to simulate bone microenvironmental conditions for the study of metastatic disease. The PLG-based composite scaffolds were used to investigate the effects of the presence of the bone mineral hydroxyapatite (HA) on the metastatic behavior of breast cancer cells in the bone microenvironment. Our findings indicate that tumor cell behavior is dramatically altered towards a more malignant and metastatic phenotype in the presence of HA. Breast cancer cells cultured in biomineralized scaffolds also showed decreased sensitivity to chemotherapeutic agents relative to control conditions. Finally, HA changed the secretory behavior of tumor cells, inducing upregulated secretion of factors responsible for the predominantly osteolytic nature of breast cancer bone metastasis. Our study shows that biomineralized scaffolds can serve as a basis for the development of biomimetic bone metastasis models. In the future, they may help to reveal novel pathways for therapeutic targeting of bone metastasis, while also providing an innovative platform for studying cancer in vitro.