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Updated: Sep 24, 2025
Patient-derived Orthotopic Xenograft Models for Human Urothelial Cell Carcinoma and Colorectal Cancer Tumor Growth and Spontaneous Metastasis
Published on: May 12, 2019
Patient-derived bladder cancer xenograft models reveal VEGF and CDK4 enhancing tumor metastasis behavior
Yong Zhao1, Mingjie An2, He Zhang1
1Division of Cancer Biology, Laboratory Animal Center, The Fourth Military Medical University Xi'an Shaanxi 710032 China changhong@fmmu.edu.cn zhangcaiqin-beibei@163.com.
Abstract:
New strategies to treat advanced bladder cancer are urgently required. A patient-derived xenograft (PDX) model has become a useful tool to evaluate chemotherapeutics and investigate personalized cancer treatment options. In this study, fresh human bladder cancer specimens (C09303 and C21391) were transplanted subcutaneously into nude mice to establish PDX models. These models well retained pathological characteristics and molecular markers of the original tumor. Primary cells derived from C09303 were cultured and perfused into the bladders of nude mice to establish orthotopic xenograft models. Evident signals of lung and kidney metastases were detected by whole-body optical imaging. Gemcitabine displayed a significant therapeutic effect on the subcutaneous or orthotopic xenograft tumors of C09303. In vitro, matrigel invasion assays showed that C09303 primary culture cells are remarkably invasive. To study the metastatic properties of C09303, we sequenced the genomes of C09303 and C21391, and found that the expression of VEGF and CDK4 was significantly upregulated, and VEGF-knockdown or CDK4-knockdown C09303 cells showed attenuated invasiveness and migration. This PDX model revealed that VEGF and CDK4 enhanced tumor metastasis behavior, suggesting them as novel molecular therapeutic targets. This framework provides a tool for research on metastasis mechanism and individualized treatment for bladder cancer.
Insights
New bladder cancer models show VEGF and CDK4 drive metastasis. Targeting these molecules may offer new therapeutic strategies for advanced bladder cancer patients.
Area of Science:
- Oncology
- Cancer Biology
- Translational Research
Background:
- Advanced bladder cancer necessitates novel treatment strategies.
- Patient-derived xenograft (PDX) models are valuable for evaluating therapies and personalized medicine.
- Understanding bladder cancer metastasis is crucial for effective treatment.
Purpose of the Study:
- To establish and characterize patient-derived xenograft (PDX) models for bladder cancer.
- To investigate the molecular mechanisms underlying bladder cancer metastasis.
- To identify potential therapeutic targets for advanced bladder cancer.
Main Methods:
- Established subcutaneous and orthotopic PDX models from human bladder cancer specimens (C09303, C21391).
- Assessed therapeutic efficacy of gemcitabine in xenograft models.
- Utilized whole-body optical imaging to detect metastasis.
- Performed matrigel invasion assays and whole-genome sequencing.
- Investigated the role of VEGF and CDK4 in metastasis via knockdown experiments.
Main Results:
- PDX models accurately recapitulated the pathological and molecular features of the primary tumors.
- Gemcitabine demonstrated significant therapeutic effects on xenograft tumors.
- VEGF and CDK4 expression were significantly upregulated in bladder cancer cells.
- Knockdown of VEGF or CDK4 attenuated the invasiveness and migration of cancer cells.
- VEGF and CDK4 were identified as key drivers of tumor metastasis.
Conclusions:
- PDX models serve as effective tools for bladder cancer research and drug evaluation.
- VEGF and CDK4 play critical roles in promoting bladder cancer metastasis.
- VEGF and CDK4 represent promising molecular targets for novel bladder cancer therapies.
- This research framework aids in studying metastasis mechanisms and developing individualized treatments for bladder cancer.
