Tissue-Engineered Models for Studies of Bone Metastasis

Patients with advanced cancers are frequently diagnosed with bone metastasis, which is an incurable condition associated with pathological bone remodeling. Despite its widespread impact, understanding of the mechanisms underlying bone metastasis remains relatively limited. While traditional cancer research approaches focus on cancer cells, increasing evidence suggests a role for their surrounding microenvironment in tumorigenesis and metastasis. Therefore, model systems recapitulating physiologically relevant cell-microenvironment interactions are needed in order to study the specific underlying signaling mechanisms. Tissue-engineered, humanized in vitro models may provide an attractive alternative to conventional cell culture and rodent models, as they offer systematic control of microenvironmental aspects relevant to basic and translational studies of bone metastasis. Here, we use breast cancer as an example to review metastasis-associated changes to the bone microenvironment and current approaches to study bone metastasis. In light of their limitations, we discuss tissue-engineered model systems of bone metastasis as a promising alternative, and describe specific design parameters that should be considered when developing such models. Collectively, engineering-inspired culture approaches will be valuable to investigate the functional contribution of the microenvironment to the development, progression, and therapy response of bone metastasis.