Reorganization of the osteocyte lacuno-canalicular network characteristics in tumor sites of an immunocompetent murine model of osteotropic cancers

Mechanosensitive osteocytes are central regulators of bone resorption and formation. However, during the formation of bone metastases, which arise as consequences of breast and prostate cancer and skew homeostatic bone remodeling to favor osteolytic, osteosclerotic or mixed lesions, only a paucity of data exists on tumor-associated osteocyte interaction. Herein, we used a suite of high-resolution imaging and histological techniques to evaluate the effect of osteotropic cancer on cortical bone microarchitecture. Confocal imaging highlighted a direct contact between tumor cells residing in the bone marrow and osteocytes. High-resolution microcomputed tomography revealed a 10-12% larger osteocyte lacuna volume in the presence of tumor cells at day 21 after intratibial injection of EO771-Luc breast and RM1-Luc prostate cancer cells. The 3D representative of the spatial distribution of cortical bone microporosity showed i) a regional accumulation of vascular canals and large lacunae with low connectivity in osteosclerotic regions of interest and ii) an absence of vascular canals and large lacunae in osteolytic regions. These findings pinpoint the relationship between the presence of tumor cells in the bone marrow microenvironment and osteocyte lacunar characteristics and cortical bone blood vessel structure.