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Updated: May 7, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
A new murine model of osteoblastic/osteolytic lesions from human androgen-resistant prostate cancer
Anaïs Fradet1, Hélène Sorel, Baptiste Depalle
1Institut National de la Santé et de la Recherche Médicale (INSERM), Unité U1033, Lyon, France ; Université de Lyon, Lyon, France.
Background:
Up to 80% of patients dying from prostate carcinoma have developed bone metastases that are incurable. Castration is commonly used to treat prostate cancer. Although the disease initially responds to androgen blockade strategies, it often becomes castration-resistant (CRPC for Castration Resistant Prostate Cancer). Most of the murine models of mixed lesions derived from prostate cancer cells are androgen sensitive. Thus, we established a new model of CRPC (androgen receptor (AR) negative) that causes mixed lesions in bone.
Methods:
PC3 and its derived new cell clone PC3c cells were directly injected into the tibiae of SCID male mice. Tumor growth was analyzed by radiography and histology. Direct effects of conditioned medium of both cell lines were tested on osteoclasts, osteoblasts and osteocytes.
Results:
We found that PC3c cells induced mixed lesions 10 weeks after intratibial injection. In vitro, PC3c conditioned medium was able to stimulate tartrate resistant acid phosphatase (TRAP)-positive osteoclasts. Osteoprotegerin (OPG) and endothelin-1 (ET1) were highly expressed by PC3c while dikkopf-1 (DKK1) expression was decreased. Finally, PC3c highly expressed bone associated markers osteopontin (OPN), Runx2, alkaline phosphatase (ALP), bone sialoprotein (BSP) and produced mineralized matrix in vitro in osteogenic conditions.
Conclusions:
We have established a new CRPC cell line as a useful system for modeling human metastatic prostate cancer which presents the mixed phenotype of bone metastases that is commonly observed in prostate cancer patients with advanced disease. This model will help to understand androgen-independent mechanisms involved in the progression of prostate cancer in bone and provides a preclinical model for testing the effects of new treatments for bone metastases.
Insights
A new Castration Resistant Prostate Cancer (CRPC) cell line was developed to model bone metastases. This model aids in understanding androgen-independent prostate cancer progression and testing new treatments.
Area of Science:
- Oncology
- Bone Metastasis Research
- Prostate Cancer Models
Background:
- Bone metastases are a common, incurable complication of advanced prostate cancer, affecting up to 80% of patients.
- While initially responsive to androgen blockade, prostate cancer frequently progresses to Castration-Resistant Prostate Cancer (CRPC).
- Existing murine models often lack the mixed bone lesion phenotype characteristic of human CRPC.
Purpose of the Study:
- To establish a novel in vivo model of CRPC with mixed bone lesions.
- To characterize the androgen receptor (AR)-negative CRPC cell line's bone-modifying capabilities.
- To provide a preclinical platform for investigating CRPC bone metastasis mechanisms.
Main Methods:
- Intratibial injection of PC3 and PC3c cells into SCID mice.
- Radiographic and histological analysis of tumor growth and bone lesions.
- In vitro assessment of PC3c conditioned medium effects on osteoclasts, osteoblasts, and osteocytes.
Main Results:
- PC3c cells induced mixed bone lesions in mice 10 weeks post-injection.
- PC3c conditioned medium stimulated osteoclast activity (TRAP-positive).
- PC3c cells exhibited altered expression of bone-related factors (increased OPG, ET1; decreased DKK1) and produced mineralized matrix.
Conclusions:
- A new AR-negative CRPC cell line (PC3c) effectively models mixed bone metastases in vivo.
- This model system is valuable for studying androgen-independent prostate cancer bone progression.
- The model offers a preclinical tool for evaluating novel therapeutic strategies for bone metastases.
