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Updated: Sep 11, 2025
A Murine Orthotopic Bladder Tumor Model and Tumor Detection System
Published on: January 12, 2017
A Double-Humanized Murine Model in Bladder Cancer: A Novel Preclinical Model for Cancer Immunology Research
Niannian Ji1,2, Zaineb Hassouneh1,2, Shaun Trecarten1,2
1Experimental Developmental Therapeutics (EDT) Program, Mays Cancer Center at UT Health MD Anderson, San Antonio, Texas, USA.
Background:
Bladder cancer (BC) ranks as the 10th leading cause of cancer-related deaths in the United States. Despite significant advancements in managing BC, including antibody-drug conjugates and immune checkpoint blockers, a significant percentage of patients fail these treatments. This underscores the pressing need to develop methods for identifying novel therapeutic targets, predicting therapy responses, and optimizing personalized treatment strategies for patients. Patient-derived xenograft (PDX) models have the potential to address these challenges. However, these models suffer from limitations, including a consistent rate of tumor acceptance, extended time for tumor growth, and the absence of the donor's immune system.
Methods:
This study aimed to address these challenges through a comprehensive comparison of different PDX implantation methods, culminating in the establishment of a PDX cell line for utilization in in vivo BC preclinical models. Flow cytometry analysis and total RNA sequencing were used for comparative analysis of original tumor tissue, PDX tumor, and PDX257S cell line.
Results:
Tumor tissue processing techniques were optimized to enhance the rate of PDX tumor acceptance and shorten the time to tumor development. Furthermore, a PDX cell line, PDX257S, was successfully established and confirmed to exhibit more aggressive and tumorigenic characteristics compared to the original donor tumor tissue. The PDX257S cell line demonstrated faster tumor growth, higher expression of human epithelial cell adhesion molecule, increased mutation burden in BC-associated genes, and significant alterations in BC-related gene expression, compared to the original tumor. The PDX257S cell line was also used to establish a double humanized BC murine model that minimized graft-versus-host disease and is a potential platform for testing novel immune therapeutics.
Conclusions:
In summary, this study offers an optimized protocol for the consistent establishment of BC PDX tumors. Furthermore, it has also established a novel double-humanized model, demonstrating the potential for drug screening and clinical prognosis in the context of BC treatment.
Insights
This study optimized bladder cancer (BC) patient-derived xenograft (PDX) models and established a new PDX cell line (PDX257S) for improved preclinical research and drug screening. A double humanized model was also developed for testing novel immunotherapeutics.
Area of Science:
- Oncology
- Preclinical Cancer Research
- Translational Medicine
Background:
- Bladder cancer (BC) is a significant cause of cancer mortality, with many patients unresponsive to current therapies.
- Novel therapeutic targets and personalized treatment strategies are urgently needed for BC.
- Patient-derived xenograft (PDX) models offer potential but have limitations in tumor acceptance, growth time, and immune system representation.
Purpose of the Study:
- To optimize PDX implantation methods for bladder cancer (BC).
- To establish a PDX cell line for in vivo preclinical models.
- To develop a double humanized BC murine model for therapeutic testing.
Main Methods:
- Comparative analysis of original tumor tissue, PDX tumor, and PDX257S cell line using flow cytometry and RNA sequencing.
- Optimization of tumor tissue processing techniques for PDX establishment.
- Development of a double humanized murine model.
Main Results:
- Optimized techniques improved PDX tumor acceptance rates and reduced tumor development time.
- The established PDX257S cell line exhibited enhanced aggressiveness, faster growth, and increased mutation burden compared to original tumor tissue.
- A double humanized BC model was created, minimizing graft-versus-host disease and enabling immune therapeutic testing.
Conclusions:
- An optimized protocol for consistent BC PDX tumor establishment was developed.
- A novel double-humanized model was established for BC drug screening and clinical prognosis.
- The PDX257S cell line and humanized model provide valuable platforms for advancing BC research.
