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Updated: Apr 19, 2026
Generation of Prostate Cancer Patient Derived Xenograft Models from Circulating Tumor Cells
Published on: October 20, 2015
Establishing prostate cancer patient derived xenografts: lessons learned from older studies
Pamela J Russell1, Peter Russell, Christina Rudduck
1Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Brisbane, Queensland, 4102,, Australia.
Background:
Understanding the progression of prostate cancer to androgen-independence/castrate resistance and development of preclinical testing models are important for developing new prostate cancer therapies. This report describes studies performed 30 years ago, which demonstrate utility and shortfalls of xenografting to preclinical modeling.
Methods:
We subcutaneously implanted male nude mice with small prostate cancer fragments from transurethral resection of the prostate (TURP) from 29 patients. Successful xenografts were passaged into new host mice. They were characterized using histology, immunohistochemistry for marker expression, flow cytometry for ploidy status, and in some cases by electron microscopy and response to testosterone. Two xenografts were karyotyped by G-banding.
Results:
Tissues from 3/29 donors (10%) gave rise to xenografts that were successfully serially passaged in vivo. Two, (UCRU-PR-1, which subsequently was replaced by a mouse fibrosarcoma, and UCRU-PR-2, which combined epithelial and neuroendocrine features) have been described. UCRU-PR-4 line was a poorly differentiated prostatic adenocarcinoma derived from a patient who had undergone estrogen therapy and bilateral castration after his cancer relapsed. Histologically, this comprised diffusely infiltrating small acinar cell carcinoma with more solid aggregates of poorly differentiated adenocarcinoma. The xenografted line showed histology consistent with a poorly differentiated adenocarcinoma and stained positively for prostatic acid phosphatase (PAcP), epithelial membrane antigen (EMA) and the cytokeratin cocktail, CAM5.2, with weak staining for prostate specific antigen (PSA). The line failed to grow in female nude mice. Castration of three male nude mice after xenograft establishment resulted in cessation of growth in one, growth regression in another and transient growth in another, suggesting that some cells had retained androgen sensitivity. The karyotype (from passage 1) was 43-46, XY, dic(1;12)(p11;p11), der(3)t(3:?5)(q13;q13), -5, inv(7)(p15q35) x2, +add(7)(p13), add(8)(p22), add(11)(p14), add(13)(p11), add(20)(p12), -22, +r4[cp8].
Conclusions:
Xenografts provide a clinically relevant model of prostate cancer, although establishing serially transplantable prostate cancer patient derived xenografts is challenging and requires rigorous characterization and high quality starting material. Xenografting from advanced prostate cancer is more likely to succeed, as xenografting from well differentiated, localized disease has not been achieved in our experience. Strong translational correlations can be demonstrated between the clinical disease state and the xenograft model.
Insights
Establishing patient-derived prostate cancer xenografts is challenging but provides clinically relevant preclinical models. Success is more likely with advanced disease, offering insights into androgen-independent prostate cancer progression.
Area of Science:
- Oncology
- Urology
- Cancer Biology
Background:
- Understanding prostate cancer progression to androgen-independence is crucial for developing new therapies.
- Preclinical testing models are essential for evaluating novel prostate cancer treatments.
- This study revisits early xenografting experiments to assess their utility and limitations in preclinical prostate cancer modeling.
Purpose of the Study:
- To evaluate the feasibility and characteristics of patient-derived prostate cancer xenografts.
- To assess the potential of xenografts as preclinical models for advanced prostate cancer.
- To investigate the relationship between xenograft behavior and the original patient's clinical disease state.
Main Methods:
- Prostate cancer tissue fragments from 29 patients were implanted into male nude mice.
- Successful xenografts were serially passaged and characterized via histology, immunohistochemistry, and flow cytometry.
- Limited karyotyping and response to castration/testosterone were assessed for select xenograft lines.
Main Results:
- Xenografts were successfully established from 10% (3/29) of patient donors.
- One xenograft line (UCRU-PR-4) derived from a patient with relapsed, castrated, and estrogen-treated cancer exhibited poorly differentiated adenocarcinoma characteristics.
- This line showed partial androgen sensitivity, with varied responses to castration in host mice.
Conclusions:
- Patient-derived xenografts can serve as clinically relevant models for prostate cancer research.
- Establishing serially transplantable xenografts is challenging, requiring rigorous characterization and high-quality tissue.
- Xenografting advanced prostate cancer is more successful than from localized disease, demonstrating translational correlations.
