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

A mouse model of prostate cancer bone metastasis in a syngeneic immunocompetent host
in vivo and ex-vivo growth kinetics of B6CaP. Growth rates of CR sublines in castrate hosts, measured as time from injection to 1.5 cm tumor size, was significantly slower than parental B6CaP cells in intact hosts (A, 42.9 vs 63.3 days, p < 0.001). Organoids retained androgen sensitivity in vitro, growing rapidly to form organoids/spheres in media containing DHT, but rarely forming small spheres without DHT (B). Three weeks after plating 105 cells as organoids, cells in media containing DHT had expanded 10-fold, but total cell number had decreased in media without DHT (C). Credit: Edward M. Schaeffer - e-schaeffer@northwestern.edu

The Research Team reports the establishment of B6Ca P, an allograft tumor line from a Hi-Myc transgenic mouse that had been backcrossed onto C57BL/6J background.

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 useful for studying mechanisms of bone metastasis and tumor immune response.

Dr. Edward M. Schaeffer from the Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA said, "Prostate cancer (PCa) is the most common non-cutaneous cancer in the United States, and is the third leading cause of cancer-related deaths in men."

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 in mice 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.

To overcome these problems, numerous genetically engineered mouse models of PCa have been developed over the years including the TRAMP model that displays PCa metastases to distant organs such as lung, but rarely to bones, a feature consistent in other models as well.

Intracardiac injection of B6Ca P results in frequent skeletal metastases, making it an excellent pre-clinical model to study the mechanisms of metastasis in PCa.

The Schaeffer Research Team concluded that, taken together, B6Ca P line overcomes two critical limitations to study the skeletal metastasis of prostate .


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More information: Simons, et al. A mouse model of prostate cancer bone metastasis in a syngeneic immunocompetent host, Oncotarget (2019). DOI: 10.18632/oncotarget.27317
Journal information: Oncotarget

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