Oncotarget

Research Papers:

A mouse model of prostate cancer bone metastasis in a syngeneic immunocompetent host

Brian W. Simons, Vishal Kothari, Benjamin Benzon, Kamyar Ghabili, Robert Hughes, Jelani C. Zarif, Ashley E. Ross, Paula J. Hurley and Edward M. Schaeffer _

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Oncotarget. 2019; 10:6845-6854. https://doi.org/10.18632/oncotarget.27317

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Abstract

Brian W. Simons1,2, Vishal Kothari4, Benjamin Benzon1, Kamyar Ghabili1, Robert Hughes1, Jelani C. Zarif3, Ashley E. Ross1,4, Paula J. Hurley1 and Edward M. Schaeffer4

1 The Brady Urological Institute, Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

2 Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

3 Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

4 Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

Correspondence to:

Edward M. Schaeffer,email: e-schaeffer@northwestern.edu

Keywords: prostate cancer; bone metastasis; murine model

Received: April 19, 2019     Accepted: October 26, 2019     Published: December 03, 2019

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.


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