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Updated: Mar 22, 2026
Generation of Prostate Cancer Patient Derived Xenograft Models from Circulating Tumor Cells
Published on: October 20, 2015
An original patient-derived xenograft of prostate cancer with cyst formation
Takeshi Yoshikawa1, Go Kobori1, Takayuki Goto1
1Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Background:
The high rate of failure of new agents in oncology clinical trials indicates a weak understanding of the complexity of human cancer. Recent understanding of the mechanisms underlying castration resistance in prostate cancer led to the development of new agents targeting the androgen receptor pathway; however, their effectiveness is limited. Hence, there is a need for experimental systems that are able to better reproduce the biological diversity of prostate cancer in preclinical settings. In this study, we established a unique patient-derived xenograft (PDX) model to identify biomarkers for treatment efficacy and resistance and better understand prostate cancer biology.
Methods:
A prostate cancer tissue sample from a Japanese patient was transplanted subcutaneously into male, severe combined immune-deficient (SCID) mice and this PDX mouse model was named KUCaP3. Sequential tumor volume changes were observed before and after castration. Androgen receptor (AR), prostate-specific antigen (PSA), and other molecular markers were examined immunohistochemically. Sequence analysis of AR was also performed to detect mutations. Proteomic analysis of cyst fluid and sera samples of KUCaP3 mice were analyzed by mass spectrometry (MS).
Results:
KUCaP3 cell line, derived from human tissue, was successfully and serially passaged in vivo with approximately 60% take rate. KUCaP3 exhibited cyst formation, showed androgen-dependent growth initially, and developed castration-resistant growth several months after castration of the mice. Immunohistochemical analysis showed that KUCaP3 was positive for AR, PSA, CK18, and α-methyl acyl-coenzyme A racemase, but negative for CK5/6 and ERG. The AR gene in KUCaP3 cells contained a substitution from CAT (histidine) to TAT (tyrosine) at the nucleotide positions corresponding to codon 875 (H875Y) in the ligand-binding domain. Chemiluminescent immunoassay revealed higher levels of PSA in cystic fluid and the serum of KUCaP3-bearing mice. MS analysis detected 23 proteins of human origin in cystic fluids of KUCaP3.
Conclusions:
We developed KUCaP3, an androgen-dependent PDX model with cyst formation. Several proteins including PSA were detected in the cystic fluid and sera of tumor-bearing mice. This original PDX model has the potential to be used as a clinically relevant model to evaluate molecular markers for prostate cancer diagnosis and treatment. Prostate 76:994-1003, 2016. © 2016 Wiley Periodicals, Inc.
Insights
A new patient-derived xenograft (PDX) model, KUCaP3, was developed to study prostate cancer biology. This model exhibits androgen-dependent and castration-resistant growth, aiding in the search for new diagnostic and treatment biomarkers.
Area of Science:
- Oncology
- Cancer Biology
- Genitourinary Cancers
Background:
- High failure rates in oncology clinical trials highlight gaps in understanding cancer complexity.
- Current androgen receptor pathway-targeted therapies for prostate cancer show limited effectiveness.
- There is a critical need for preclinical models that better represent prostate cancer's biological diversity.
Purpose of the Study:
- To establish a unique patient-derived xenograft (PDX) model for prostate cancer research.
- To identify potential biomarkers for treatment efficacy and resistance.
- To gain deeper insights into prostate cancer biology.
Main Methods:
- A patient-derived xenograft (PDX) model, KUCaP3, was created by transplanting Japanese prostate cancer tissue into SCID mice.
- Tumor growth dynamics were monitored before and after castration.
- Immunohistochemistry, AR sequencing, and mass spectrometry were employed to analyze molecular markers, AR mutations, and protein expression in cyst fluid and serum.
Main Results:
- The KUCaP3 model demonstrated successful serial passaging in vivo with a 60% take rate.
- KUCaP3 exhibited androgen-dependent growth, cyst formation, and subsequent development of castration resistance.
- The model was positive for AR, PSA, CK18, and α-methyl acyl-coenzyme A racemase, with an H875Y mutation in the AR gene. Elevated PSA levels were detected in cyst fluid and serum.
Conclusions:
- KUCaP3 is a novel androgen-dependent PDX model with cyst-forming capabilities.
- The model facilitates the detection of proteins like PSA in cystic fluid and serum.
- This PDX model holds promise for evaluating molecular markers in prostate cancer diagnosis and treatment.
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