Abstract 1597: A novel preclinical model of prostate cancer bone metastasis derived from a human primary tumor

Abstract

Abstract Background: Prostate cancer is frequently associated with bone metastases which are the main cause of morbidity and mortality for this tumor. Animal models are important tools to investigate the pathogenesis and develop treatment strategies for bone metastases in humans. However there are few animal models that recapitulate spontaneous clinical bone metastases. We recently obtained the new prostate cell line IGR-CaP1 derived from primary epithelial prostate cancer that has been characterize in vitro. Methods: The IGR-CaP1 cell line was stably transduced with a luciferase expressing viral vector to monitor tumor growth by bioluminescence imaging (BLI) in male nude mice. Bone lesions were observed after direct intratibial injections of 5×105 luciferase-expressing IGR-CaP1 cells and after injection of 106 cells into the left cardiac ventricle of mice. Bone metastases were detected by bioluminescence imaging and were evaluated by both Computerized Tomography (CT) and micro Single-Photon Emission Computed Tomography (SPECT) measuring the bone fixation of 99Tc methylenediphosphonate (m99Tc-MDP). Results: In contrast with the widely used PC3 preclinical model showing only osteolytic activity after bone injection, high resolution CT scan showed both lytic lesions in the cortical bone and osteoblastic lesions in the trabecular bone in the IGR-CaP1-injected mice 5 weeks after injection. The mixed nature of the lesions and the intensive bone remodeling were confirmed by bone scintigraphy with a ∼5 fold increase in m99Tc-MDP fixation in injected tibia versus control tibia. Intracardiac injection led to bone metastasis mainly localized in the spinal column, fore and hind limbs and in the mandible. Immunohistochemistry confirmed the presence of these bone metastases and showed high expression of vimentin in metastatic tumor cells. In this model, we are currently analyzing by RT-PCR, the expression of a 25-gene signature that corresponds to genes highly expressed in human bone metastases. Conclusion: IGR-CaP1 is a unique model issued from a primary tumor able to reconstitute human prostate adenocarcinoma in animals and provide bone metastases. This model provides a novel means for identifying and understanding mechanisms that contribute to bone metastasis and allows for preclinical testing of new anticancer therapies, specifically bone-targeting therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1597. doi:10.1158/1538-7445.AM2011-1597