Abstract
We report the establishment of B6CaP, an allograft tumor line from a Hi-Myc transgenic mouse that had been backcrossed onto C57BL/6J background. This tumor line grows subcutaneously in wildtype C57BL/6J immunocompetent mice, expresses AR, and has a luminal cytokeratin profile. When digested into single cells and injected via intracardiac injection, B6CaP produces metastatic widespread metastases including frequent bone lesions. Metastatic lesions occur most often in the femur, spine, and skull, and have a mixed osteolytic/osteoblastic phenotype. B6CaP allografts are androgen dependent, and regress after castration. However, castration resistant tumors regrow after 4–6 months and can be maintained as androgen-independent clones. This is the first example of a prostate-derived tumor line that shows frequent metastasis to bone and grows in an immunocompetent host, making this model useful for studying mechanisms of bone metastasis and tumor immune response.
Highlights
Prostate cancer (PCa) is the most common noncutaneous cancer in the United States, and is the third leading cause of cancer-related deaths in men [1]
Given that majority of clinical cases of prostate cancers are adenocarcinoma www.oncotarget.com with limited neuroendocrine differentiation, it is critical to develop animal model systems that closely recapitulate human prostate adenocarcinoma and subsequent metastatic events seen in the clinics
The Hi-Myc mice showed the development of prostatic intraepithelial neoplasia (PIN) and its progression to invasive carcinoma, metastasis was absent in this model [10]
Summary
Prostate cancer (PCa) is the most common noncutaneous cancer in the United States, and is the third leading cause of cancer-related deaths in men [1]. Animal models of cancer allow the study of molecular mechanisms of disease progression and test new treatments across the disease sites; but an uncommon occurrence of spontaneous prostate cancer in mice [3] and a lack of animal model systems that closely recapitulate the human PCa hampers the mechanistic understanding of metastatic progression and development of effective treatments for advanced PCa. While xenografts of human cell lines in immunodeficient mice remain the most commonly used models, PCa cell lines rarely metastasize from subcutaneous grafts, with an exception of a few cell lines that metastasize when injected orthotopically [4]. Given that majority of clinical cases of prostate cancers are adenocarcinoma www.oncotarget.com with limited neuroendocrine differentiation, it is critical to develop animal model systems that closely recapitulate human prostate adenocarcinoma and subsequent metastatic events seen in the clinics
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