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Updated: Jun 19, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 19, 2013
Androgen receptor-negative human prostate cancer cells induce osteogenesis in mice through FGF9-mediated mechanisms
Zhi Gang Li1, Paul Mathew, Jun Yang
1Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA.
Abstract:
In prostate cancer, androgen blockade strategies are commonly used to treat osteoblastic bone metastases. However, responses to these therapies are typically brief, and the mechanism underlying androgen-independent progression is not clear. Here, we established what we believe to be the first human androgen receptor-negative prostate cancer xenografts whose cells induced an osteoblastic reaction in bone and in the subcutis of immunodeficient mice. Accordingly, these cells grew in castrated as well as intact male mice. We identified FGF9 as being overexpressed in the xenografts relative to other bone-derived prostate cancer cells and discovered that FGF9 induced osteoblast proliferation and new bone formation in a bone organ assay. Mice treated with FGF9-neutralizing antibody developed smaller bone tumors and reduced bone formation. Finally, we found positive FGF9 immunostaining in prostate cancer cells in 24 of 56 primary tumors derived from human organ-confined prostate cancer and in 25 of 25 bone metastasis cases studied. Collectively, these results suggest that FGF9 contributes to prostate cancer-induced new bone formation and may participate in the osteoblastic progression of prostate cancer in bone. Androgen receptor-null cells may contribute to the castration-resistant osteoblastic progression of prostate cancer cells in bone and provide a preclinical model for studying therapies that target these cells.
Insights
This study identifies Fibroblast Growth Factor 9 (FGF9) as a key driver in androgen receptor-negative prostate cancer bone metastasis. FGF9 promotes new bone formation, offering a potential therapeutic target for castration-resistant prostate cancer progression.
Area of Science:
- Oncology
- Bone Metastasis Research
- Molecular Biology
Background:
- Androgen blockade is a common treatment for prostate cancer bone metastases, but responses are often short-lived.
- The mechanisms driving androgen-independent progression in prostate cancer remain unclear.
- Osteoblastic bone metastases are a significant challenge in advanced prostate cancer.
Purpose of the Study:
- To establish and characterize androgen receptor-negative prostate cancer xenografts that induce osteoblastic reactions.
- To investigate the role of Fibroblast Growth Factor 9 (FGF9) in prostate cancer-induced bone formation.
- To explore FGF9 as a potential therapeutic target in castration-resistant prostate cancer bone metastasis.
Main Methods:
- Development of human androgen receptor-negative prostate cancer xenografts in immunodeficient mice.
- Assessment of tumor growth in both castrated and intact male mice.
- In vitro and in vivo assays to evaluate the effect of FGF9 on osteoblast proliferation and bone formation.
- Immunohistochemical analysis of FGF9 expression in primary prostate tumors and bone metastases.
Main Results:
- Established novel androgen receptor-negative prostate cancer xenografts that induce osteoblastic reactions and grow independently of androgen status.
- Identified overexpression of FGF9 in these xenografts, correlating with increased osteoblast proliferation and new bone formation.
- Demonstrated that FGF9 neutralization significantly reduced bone tumor size and formation.
- Found positive FGF9 immunostaining in a substantial proportion of primary prostate tumors and all studied bone metastasis samples.
Conclusions:
- FGF9 plays a critical role in promoting osteoblastic new bone formation in prostate cancer bone metastasis.
- Androgen receptor-null prostate cancer cells and FGF9 signaling are implicated in castration-resistant osteoblastic progression.
- These findings provide a preclinical model for studying therapies targeting FGF9 in advanced prostate cancer.
