Treatment of transforming growth factor-beta-insensitive mouse Renca tumor by transforming growth factor-beta elimination.

Abstract

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.

• Authors: Kent Perry, Larry Wong, Victoria Liu, Irwin Park, Qiang Zhang, Varun Rejen, Xuemei Huang, Norm D Smith, Borko Jovanovic, Scott Lonning, Beverly A Teicher, Chung Lee
• Journal: Urology (Urology) Vol. 72 Issue 1 Pg. 225-9 (Jul 2008) ISSN: 1527-9995 [Electronic] United States
• PMID: 18295867 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Transforming Growth Factor beta

Topics

• Animals
• Carcinoma, Renal Cell (metabolism, pathology, secondary, therapy)
• Cell Line, Tumor
• Cell Proliferation
• In Vitro Techniques
• Kidney Neoplasms (metabolism, pathology, therapy)
• Lung Neoplasms (secondary)
• Male
• Mice
• Mice, Inbred BALB C
• Neoplasm Transplantation
• Transfection
• Transforming Growth Factor beta (immunology, physiology)