Background

Bone metastasis research is extremely limited due to the lack of efficient and faithful experimental models (Weigelt et al., 2005; Simmons et al., 2015). Current in vivo bone metastasis models require extensive surgical labor, rendering high-throughput assays impossible (Blouin et al., 2005; Simmons et al., 2015; Kuchimaru et al., 2018). In vitro systems, on the other hand, cannot recapitulate the cellular and molecular complexity of the bone microenvironment (Taubenberger, 2014; Cunningham and You, 2015). To complement existing systems, we developed the BICA platform to investigate mechanisms involved in bone colonization and to rapidly test drug efficacies on bone metastases (Wang et al., 2015; Yu et al., 2016).

BICA is performed by selectively delivering cancer cells into the hind limbs of mice via the external iliac artery followed by extracting and fragmenting the cancer-containing bones and exposing the bone fragments to ex vivo cultures (Wang et al., 2015; Yu et al., 2016). The cancer cell growth in BICA will then be determined using bioluminescence signals. Our previous work has established that BICA recapitulates in vivo bone metastases characteristics, including the microenvironmental niche, gene expression profile, metastatic growth kinetics, and therapeutic responses (Wang et al., 2015). Therefore, BICA as a reliable and high-throughput experimental platform to investigate bone metastases processes in breast cancer and prostate cancer or even other cancer types that can potentially give rise to bone metastases.