Development and validation of animal model for study of metastatic bone tumor

Bone is one of the most favored sites of tumor metastasis. However, the existent animal models developed to understand mechanism of occurrence and progress of metastatic bone tumor generally showed difficulties of reproducibility and performance of longitudinal study, and inaccuracy of validation. The aim of this study was, therefore, to newly develop and accurately validate an animal model for study of metastatic bone tumor with overcome of the limitations shown in the existent animal models. Eighteen female Sprague-Dawley rats (12 weeks old, 250+7 g) were randomly allocated in Sham and Tumor groups. W256 breast cancer cell was inoculated in the right femur of the rat for Tumor group, while 0.9% NaCl was injected for Sham group. Urine was collected by metabolic cages for DPD (deoxypyridinoline) test in order to evaluate bone resorption at 0, 4, 8, 12 weeks after surgery. At the same time, the right hind limbs of all rats were scanned by in-vivo micro-computered tomography (CT) to identify tumor-mediated bone destruction driven from metastatic bone tumor. Finally, positron emission tomography was examined to directly identify existence of tumor cells inoculated in the bone. DPD test showed that bone resorption markedly increased in the bone of Tumor group compared to that of Sham group (p<0.05). In-vivo micro-computed tomography showed that there were significant bone losses and X-ray attenuation values in the bone of Tumor group compared to that of Sham group after surgery. In addition, tumor cells were directly identified in the bone of Tumor group by positron emission tomography, not in the bone of Sham group. The results indicated that the developed animal model might be confidential and reasonable to performances of studies related to metastatic bone tumor, with easy reproducibility, accuracy of validation, and suitability to performance of longitudinal study. To our knowledge, this study may prove valuable as the first development of the animal model overcoming the limitations shown in the existent animal models. The animal model developed in the present study may be useful for further metastatic bone tumor studies as mentioned.