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Updated: Jul 7, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Treatment of transforming growth factor-beta-insensitive mouse Renca tumor by transforming growth factor-beta
Kent Perry1, Larry Wong, Victoria Liu
1Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Objectives:
The mouse renal cell carcinoma line, Renca, is insensitive to transforming growth factor-beta (TGF-beta) in vitro. The present study was conducted to determine whether removal of TGF-beta from these tumor cells would inhibit tumor progression in vivo.
Methods:
TGF-beta elimination was accomplished either by administration of neutralizing TGF-beta antibody into mice receiving intravenous injection of Renca tumor cells or infection of TGF-beta antisense expression vector into these tumor cells before subcutaneous injection into recipient mice.
Results:
Although a low dose of TGF-beta antibody (5 mg/kg every 3 days) was without any effect, a high dose of TGF-beta antibody (50 mg/kg every 3 days), administered to recipient mice, resulted in a significant reduction in lung metastasis and was accompanied by increased apoptosis in the tumor cells. When the tumor cells were transfected with a TGF-beta1 antisense expressing vector, a significant reduction occurred in the tumor incidence, as well as the tumor burden. However, in nude mice, cells with reduced TGF-beta1 production grew almost as well as did the unmodified Renca cells, suggesting that the host's immune system might play an antitumor role.
Conclusions:
These results indicate that progression of Renca tumor can be inhibited by eliminating TGF-beta from the tumor cells. Our results also suggest that, although insensitive to TGF-beta under in vitro conditions, Renca tumors could be inhibited by TGF-beta removal through the systemic host environment.
Insights
Eliminating transforming growth factor-beta (TGF-beta) from Renca tumor cells significantly inhibited tumor progression in vivo. This suggests TGF-beta removal can be a strategy to control Renca tumors, even when cells are TGF-beta insensitive in vitro.
Area of Science:
- Oncology
- Cancer Biology
- Immunology
Background:
- The Renca mouse renal cell carcinoma line exhibits in vitro resistance to transforming growth factor-beta (TGF-beta).
- Understanding the role of TGF-beta in Renca tumor progression in vivo is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate whether inhibiting TGF-beta signaling in Renca tumor cells can impede tumor growth and metastasis in a living organism.
- To explore the potential of TGF-beta targeted therapies for renal cell carcinoma.
Main Methods:
- Renca tumor cells were administered to mice, with TGF-beta inhibited either by systemic administration of a neutralizing TGF-beta antibody or by pre-treatment of tumor cells with a TGF-beta antisense expression vector.
- Tumor incidence, burden, lung metastasis, and apoptosis were assessed in treated and control groups.
Main Results:
- High-dose TGF-beta antibody treatment significantly reduced lung metastasis and increased tumor cell apoptosis.
- Transfection with a TGF-beta1 antisense vector markedly decreased tumor incidence and burden.
- In immunodeficient nude mice, TGF-beta1-reduced cells showed growth similar to unmodified cells, indicating a potential role for the host immune system.
Conclusions:
- Inhibition of TGF-beta effectively suppresses Renca tumor progression in vivo, despite in vitro TGF-beta insensitivity.
- Targeting TGF-beta in the tumor microenvironment represents a viable therapeutic approach for Renca, potentially enhanced by a functional host immune system.
