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Updated: May 24, 2025
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
New mouse models for exploring renal tumor extension into the inferior vena cava
Xiubin Li1, Huaikang Li1,2, Xupeng Zhao1,3
1Department of Urology, The Third Medical Center, Chinese PLA General Hospital, Beijing, China.
Abstract:
Renal tumors with inferior vena cava tumor thrombus (IVCTT) remain a challenge in urology. However, in vivo models remain unavailable, which hampers the elucidation of its pathogenesis, identification of therapeutic targets, and screening for effective drugs. In this study, we initially develop two IVCTT models in BALB/c and BALB/c-nu/nu mice using the mouse Renca cell line. The pathological features and immune microenvironment of IVCTT in immunocompetent mice closely resembles those observed in humans. Single-cell transcriptome sequencing, immunohistochemistry and multiplex immunohistochemistry reveal a predominance of monocytes, macrophages, and neutrophils within IVCTT, mirroring the cellular composition of the human IVCTT; however, fewer lymphocytes are observed. The IVCTT in immunodeficient mice progresses much faster than in immunocompetent mice. More importantly, we successfully use the human tumor cell line on the BALB/c nu/nu mice to create an IVCTT model. The proposed in vivo models mimic the progression of renal tumors with IVCTT, clarify that the immune system can inhibit tumor thrombus progression, and provide tools for subsequent mechanistic research and translational preclinical studies.
Insights
Researchers developed novel in vivo models for renal tumors with inferior vena cava tumor thrombus (IVCTT). These models reveal the immune system
Area of Science:
- Urology
- Oncology
- Immunology
- Translational Research
Background:
- Renal tumors with inferior vena cava tumor thrombus (IVCTT) present significant clinical challenges.
- The lack of suitable in vivo models hinders research into IVCTT pathogenesis, therapeutic targets, and drug screening.
Purpose of the Study:
- To develop and characterize novel in vivo models for renal tumors with IVCTT.
- To investigate the role of the immune microenvironment in IVCTT progression.
- To provide preclinical tools for studying IVCTT.
Main Methods:
- Development of two IVCTT mouse models using the Renca cell line in BALB/c and BALB/c-nu/nu mice.
- Pathological analysis and immune microenvironment characterization using single-cell transcriptome sequencing, immunohistochemistry, and multiplex immunohistochemistry.
- Comparison of IVCTT progression in immunocompetent versus immunodeficient mice.
Main Results:
- IVCTT models in immunocompetent mice closely mimic human pathological features and immune composition (monocytes, macrophages, neutrophils).
- IVCTT progressed significantly faster in immunodeficient mice, indicating an inhibitory role of the immune system.
- A human IVCTT model was successfully established in immunodeficient mice.
Conclusions:
- The developed in vivo models accurately mimic human IVCTT progression.
- The immune system plays a crucial role in inhibiting tumor thrombus progression.
- These models offer valuable tools for future mechanistic and translational research in IVCTT.
