Optimization and Characterization of a Bone Culture Model to Study Prostate Cancer Bone Metastasis

Abstract

Abstract Nearly 90% of patients with advanced prostate cancer manifest bone metastases. Distinct from the osteolytic metastasis mostly observed in other cancer types, prostate cancer bone metastasis is typically more osteoblastic, which is relatively understudied due to the lack of reliable and efficient models to resemble the indolent cellular growth and complexity of metastatic progression. In our previous studies, we developed bone-in-culture array (BICA) to primarily model the osteoblast-involved, pre-osteolytic stage of breast cancer bone metastasis. Given that the progression of prostate cancer bone metastasis is largely osteoblastic, it is reasonable to speculate that the original BICA model can be adjusted to investigate prostate cancer bone metastases. In this study, we refined BICA by reducing the surgical labor and improving its reproducibility and capacity. The optimized BICA can successfully recapitulate important features of prostate cancer bone metastasis such as the osteoblastic phenotype, indolent growth, cancer–niche interactions, and response to hormones. Our efforts address the long-standing need for reliable and efficient models to study prostate cancer bone metastasis.