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Abstract：
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.
摘要：
机械敏感性骨细胞是骨吸收和形成的中心调节因子。然而,在骨转移的形成过程中，这是由于乳腺癌和前列腺癌的后果以及倾斜的体内平衡的骨骼重塑而有利于溶骨，骨硬化或混合病变，关于肿瘤相关骨细胞相互作用的数据很少.在这里，我们使用了一套高分辨率成像和组织学技术来评估促骨癌对皮质骨微结构的影响.共聚焦成像强调了骨髓中肿瘤细胞与骨细胞之间的直接接触。高分辨率显微计算机断层扫描显示，在胫骨内注射EO771-Luc乳腺癌和RM1-Luc前列腺癌细胞后第21天，存在肿瘤细胞的骨细胞腔隙体积增加了10-12％。皮质骨微孔的空间分布的3D代表显示：i）在感兴趣的骨硬化区域中，血管管和大腔隙的区域积累，连通性低，以及ii）在溶骨区域中没有血管管和大腔隙。这些发现明确了骨髓微环境中肿瘤细胞的存在与骨细胞腔隙特征和皮质骨血管结构之间的关系。
