From breast cancer cell homing to the onset of early bone metastasis: the role of bone (re)modeling in early lesion formation

Breast cancer often metastasizes to bone causing osteolytic lesions. Structural and biophysical changes are rarely studied, yet are hypothesized to influence metastatic progression. Here, we developed a mouse model of early bone metastasis and multimodal 3D imaging to quantify cancer cell homing, dynamic bone (re)modeling and onset of bone metastasis. Using 3D light sheet fluorescence microscopy, we show eGFP+ cancer cells and small clusters in 3D (intact) bones. We detect early bone lesions using time-lapse in vivo microCT and reveal altered bone (re)modeling in absence of detectable lesions. With a new microCT image analysis tool, we detect and track the growth of early bone lesions over time. We show that cancer cells home in all bone compartments, while osteolytic lesions are only detected in the metaphysis, a region of high (re)modeling. Our study provides novel insights of dynamic bone (re)modeling as a driver during the early phase of metastasis.