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A preclinical xenograft model of prostate cancer using human tumors

Abstract

Most cases of prostate cancer are now diagnosed as moderate-grade localized disease. These tumor specimens are important tools in the discovery and translation of prostate cancer research; however, unlike more advanced tumors, they are notoriously difficult to grow in the laboratory. We developed a system for efficiently xenografting localized human prostate cancer tissue, and we adapted this protocol to study the interactions between the specific subsets of epithelial and stromal cells. Fresh prostate tissues or isolated epithelial cells are recombined with mouse seminal vesicle mesenchyme (SVM) and grafted under the renal capsule of immunodeficient mice for optimum growth and survival. Alternatively, mouse mesenchyme can be replaced with human prostate fibroblasts in order to determine their contribution to tumor progression. Grafts can be grown for several months to determine the effectiveness of novel therapeutic compounds when administered to host mice, thereby paving the way for personalizing the treatment of individual prostate cancers.

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Figure 1: Schematic overview of the protocol.
Figure 2: Primary cultures of prostate fibroblasts.
Figure 3: Isolation of mouse SVM.
Figure 4: Analysis of prostate grafts.

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Acknowledgements

We would like to thank L. Harewood and M. Simms for providing specimens, A. Meeker and D. Berman for invaluable advice in developing the protocol, S. Hayward for the generous gift of BPH-1 cells and J. Barlow for help in drafting the manuscript. Funding was obtained from the Australian National Health and Medical Research Council (Fellowship to M.G.L.: 1035721, Project Grant: 606492, Enabling Grant: 614296), the Prostate Cancer Foundation of Australia (November Young Investigator Grants to M.G.L. and R.A.T.), the Victorian Cancer Agency (CAPTIV), Yorkshire Cancer Research Programme Support (N.J.M. and A.T.C.) and the Peter and Lyndy White Foundation.

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All the authors contributed to protocol development; J.P., S.N., M.M.P., D.W.P. and M.F. acquired, processed or analyzed the surgical specimens; R.T., B.N., M.G.R. and H.W. performed and analyzed experiments; M.G.L., R.A.T., R.T., A.T.C., N.J.M. and G.P.R. wrote the paper.

Corresponding author

Correspondence to Gail P Risbridger.

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The authors declare no competing financial interests.

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Lawrence, M., Taylor, R., Toivanen, R. et al. A preclinical xenograft model of prostate cancer using human tumors. Nat Protoc 8, 836–848 (2013). https://doi.org/10.1038/nprot.2013.043

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