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

Urology. 2008 Jul;72(1):225-9. doi: 10.1016/j.urology.2007.11.091. Epub 2008 Mar 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Transforming Growth Factor beta