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Updated: Aug 6, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 19, 2013
Hormone-refractory prostate cancer in the Lobund-Wistar rat
Morris Pollard1, Mark A Suckow
1Lobund Institute, University of Notre Dame, Notre Dame, IN 46556, USA. mpollard@nd.edu
Abstract:
Research on cancer prevention and therapy must focus on the refractory disease, the fatal end-stage of cancer that develops in patients with organ-related solid tumors. Refractory cancers develop spontaneously in advanced-stage tumors or in relapsed cases after failed therapy. Because neither prevention nor therapy is currently feasible, refractory cancer is a major impediment to survival. There is a great need for an animal model of prostate cancer (PC), one that develops cancer from initial premalignant to the terminal refractory stages. We describe here a model of hormone-refractory prostate cancer (HRPC) that develops spontaneously through two stages by endogenous mechanisms in the Lobund-Wistar (LW) rat. The early premalignant, testosterone (T)-dependent stage is promoted by high levels of endogenous T, and up to age 12 months is reversible by T deprivation; without this intervention, the tumorigenic process progresses to the refractory stage, which is highly aggressive and does not respond to T deprivation or to a wide range of therapies. Initial refractory tumors are palpable at approximately 18 months of age. As they continue to grow, the tumors express characteristics seen in refractory cancers in humans (i.e., hypoxia, expression of hypoxia-inducible factors, and metastasis). Chemically induced HRPCs in LW rats manifest the same two developmental stages, but with shorter latency periods. A transplantable, metastasizing cell line (PAIII) was derived from a germfree LW rat with advanced-stage cancer. Both spontaneous and chemically induced autochthonous HRPC model systems serve as outstanding models for studies on the prevention and therapy of refractory cancer.
Insights
A new animal model for hormone-refractory prostate cancer (HRPC) in Lobund-Wistar rats mimics human disease progression. This model is crucial for developing effective prevention and therapy strategies for advanced-stage cancer.
Area of Science:
- Oncology
- Animal Models
- Cancer Research
Background:
- Refractory cancer, the fatal end-stage of solid tumors, presents a significant challenge in patient survival due to a lack of effective prevention and therapy.
- Developing a reliable animal model for prostate cancer (PC) that progresses from premalignant to refractory stages is essential for advancing research.
Purpose of the Study:
- To describe a novel spontaneous and chemically induced animal model of hormone-refractory prostate cancer (HRPC) in Lobund-Wistar (LW) rats.
- To establish a model that recapitulates the two-stage development of HRPC, mirroring human disease progression.
Main Methods:
- Spontaneous development of HRPC in LW rats, characterized by a testosterone (T)-dependent premalignant stage and a subsequent refractory stage.
- Chemically induced HRPC in LW rats to investigate accelerated disease progression.
- Derivation of a transplantable, metastasizing cell line (PAIII) from a germfree LW rat with advanced HRPC.
Main Results:
- The spontaneous HRPC model progresses through distinct premalignant and refractory stages, with refractory tumors appearing around 18 months.
- Refractory tumors exhibit characteristics of human refractory cancers, including hypoxia, expression of hypoxia-inducible factors, and metastasis.
- Chemically induced HRPC models show similar two-stage development but with reduced latency periods.
Conclusions:
- The developed spontaneous and chemically induced HRPC models in LW rats are valuable tools for studying refractory cancer.
- These models provide a platform for investigating novel prevention and therapeutic strategies against aggressive, treatment-resistant prostate cancer.
