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Updated: Jul 11, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Identification of Toll-like receptor 3 as a potential therapeutic target in clear cell renal cell carcinoma
Teppei Morikawa1, Akira Sugiyama, Haruki Kume
1Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Japan.
Purpose:
Renal cell carcinoma (RCC) is one of the most drug-refractory cancers. The aim of this study is to discover a novel therapeutic target molecule for clear cell RCC (CCRCC), which accounts for the majority of RCC.
Experimental Design:
Gene expression profiles of 27 CCRCCs and 9 normal kidney tissues as well as 15 various adult normal tissues were examined by Affymetrix U133 Plus 2.0 arrays. Among the 34 genes specifically up-regulated in CCRCC, overexpression of Toll-like receptor 3 (TLR3) mRNA and its protein was validated by quantitative reverse transcription-PCR, immunoblot, and immunohistochemistry. The effects of TLR3 signaling on in vitro cell growth were examined.
Results:
TLR3 gene was highly expressed in CCRCC, with only limited expression in a panel of normal tissues. On immunohistochemical analysis using a monoclonal antibody against TLR3, overexpression of TLR3 was observed in 139 of 189 (73.5%) cases of CCRCC as well as in lung metastatic CCRCC (6 of 8), whereas TLR3 expression was entirely absent in chromophobe RCC (0 of 8). Polyinosinic-polycytidilic acid, a TLR3 ligand, exerted a growth-inhibitory effect against RCC cells in a TLR3-dependent manner. Moreover, a combination of polyinosinic-polycytidilic acid and IFNalpha exerted a synergistic growth-inhibitory effect against Caki-1 RCC cells.
Conclusions:
This is the first report that TLR3 is overexpressed in CCRCC. These observations suggest that TLR3 pathway may represent a novel therapeutic target in CCRCC.
Insights
Toll-like receptor 3 (TLR3) is overexpressed in clear cell renal cell carcinoma (ccRCC), a common kidney cancer. Targeting the TLR3 pathway shows promise as a novel therapeutic strategy for ccRCC treatment.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Renal cell carcinoma (RCC) is a drug-refractory cancer.
- Clear cell RCC (ccRCC) constitutes the majority of RCC cases.
- Identifying novel therapeutic targets is crucial for improving ccRCC treatment outcomes.
Purpose of the Study:
- To discover a novel therapeutic target molecule for ccRCC.
- To investigate the role of Toll-like receptor 3 (TLR3) in ccRCC pathogenesis.
- To evaluate the potential of the TLR3 pathway as a therapeutic target in ccRCC.
Main Methods:
- Gene expression profiling of ccRCC and normal kidney/tissue samples using Affymetrix arrays.
- Validation of TLR3 mRNA and protein overexpression in ccRCC via quantitative RT-PCR, immunoblotting, and immunohistochemistry.
- Assessment of TLR3 signaling effects on in vitro ccRCC cell growth and response to TLR3 ligands.
Main Results:
- TLR3 gene and protein were significantly overexpressed in ccRCC compared to normal tissues.
- TLR3 overexpression was observed in 73.5% of ccRCC cases and metastatic ccRCC, but absent in chromophobe RCC.
- TLR3 ligand (polyinosinic-polycytidilic acid) demonstrated TLR3-dependent growth inhibition of RCC cells, with synergistic effects when combined with IFNalpha.
Conclusions:
- This study is the first to report TLR3 overexpression in ccRCC.
- The TLR3 pathway represents a potential novel therapeutic target for ccRCC.
- Targeting TLR3 may offer a new strategy for treating this challenging kidney cancer.
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