Treatment of Transforming Growth Factor-Beta-Insensitive Mouse Renca Tumor by Transforming Growth Factor-Beta Elimination

Kent T Perry Jr, Larry Wong, Victoria Liu, Irwin Park, Qiang Zhang, Varun Rejen, Xuemei Huang, Norm D. Smith, Borko Jovanovic, Scott Lonning, Beverly A. Teicher, Chung Lee*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objectives: The mouse renal cell carcinoma line, Renca, is insensitive to transforming growth factor-beta (TGF-β) in vitro. The present study was conducted to determine whether removal of TGF-β from these tumor cells would inhibit tumor progression in vivo. Methods: TGF-β elimination was accomplished either by administration of neutralizing TGF-β antibody into mice receiving intravenous injection of Renca tumor cells or infection of TGF-β antisense expression vector into these tumor cells before subcutaneous injection into recipient mice. Results: Although a low dose of TGF-β antibody (5 mg/kg every 3 days) was without any effect, a high dose of TGF-β 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-β1 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-β1 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-β from the tumor cells. Our results also suggest that, although insensitive to TGF-β under in vitro conditions, Renca tumors could be inhibited by TGF-β removal through the systemic host environment.

Original languageEnglish (US)
Pages (from-to)225-229
Number of pages5
JournalUrology
Volume72
Issue number1
DOIs
StatePublished - Jul 1 2008

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Transforming Growth Factor beta
Neoplasms
Therapeutics
Antibodies
Subcutaneous Injections
Tumor Burden
Renal Cell Carcinoma
Nude Mice
Intravenous Injections
Immune System
Apoptosis
Neoplasm Metastasis
Cell Line
Lung

ASJC Scopus subject areas

  • Urology

Cite this

Perry Jr, Kent T ; Wong, Larry ; Liu, Victoria ; Park, Irwin ; Zhang, Qiang ; Rejen, Varun ; Huang, Xuemei ; Smith, Norm D. ; Jovanovic, Borko ; Lonning, Scott ; Teicher, Beverly A. ; Lee, Chung. / Treatment of Transforming Growth Factor-Beta-Insensitive Mouse Renca Tumor by Transforming Growth Factor-Beta Elimination. In: Urology. 2008 ; Vol. 72, No. 1. pp. 225-229.
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abstract = "Objectives: The mouse renal cell carcinoma line, Renca, is insensitive to transforming growth factor-beta (TGF-β) in vitro. The present study was conducted to determine whether removal of TGF-β from these tumor cells would inhibit tumor progression in vivo. Methods: TGF-β elimination was accomplished either by administration of neutralizing TGF-β antibody into mice receiving intravenous injection of Renca tumor cells or infection of TGF-β antisense expression vector into these tumor cells before subcutaneous injection into recipient mice. Results: Although a low dose of TGF-β antibody (5 mg/kg every 3 days) was without any effect, a high dose of TGF-β 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-β1 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-β1 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-β from the tumor cells. Our results also suggest that, although insensitive to TGF-β under in vitro conditions, Renca tumors could be inhibited by TGF-β removal through the systemic host environment.",
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Treatment of Transforming Growth Factor-Beta-Insensitive Mouse Renca Tumor by Transforming Growth Factor-Beta Elimination. / Perry Jr, Kent T; Wong, Larry; Liu, Victoria; Park, Irwin; Zhang, Qiang; Rejen, Varun; Huang, Xuemei; Smith, Norm D.; Jovanovic, Borko; Lonning, Scott; Teicher, Beverly A.; Lee, Chung.

In: Urology, Vol. 72, No. 1, 01.07.2008, p. 225-229.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Treatment of Transforming Growth Factor-Beta-Insensitive Mouse Renca Tumor by Transforming Growth Factor-Beta Elimination

AU - Perry Jr, Kent T

AU - Wong, Larry

AU - Liu, Victoria

AU - Park, Irwin

AU - Zhang, Qiang

AU - Rejen, Varun

AU - Huang, Xuemei

AU - Smith, Norm D.

AU - Jovanovic, Borko

AU - Lonning, Scott

AU - Teicher, Beverly A.

AU - Lee, Chung

PY - 2008/7/1

Y1 - 2008/7/1

N2 - Objectives: The mouse renal cell carcinoma line, Renca, is insensitive to transforming growth factor-beta (TGF-β) in vitro. The present study was conducted to determine whether removal of TGF-β from these tumor cells would inhibit tumor progression in vivo. Methods: TGF-β elimination was accomplished either by administration of neutralizing TGF-β antibody into mice receiving intravenous injection of Renca tumor cells or infection of TGF-β antisense expression vector into these tumor cells before subcutaneous injection into recipient mice. Results: Although a low dose of TGF-β antibody (5 mg/kg every 3 days) was without any effect, a high dose of TGF-β 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-β1 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-β1 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-β from the tumor cells. Our results also suggest that, although insensitive to TGF-β under in vitro conditions, Renca tumors could be inhibited by TGF-β removal through the systemic host environment.

AB - Objectives: The mouse renal cell carcinoma line, Renca, is insensitive to transforming growth factor-beta (TGF-β) in vitro. The present study was conducted to determine whether removal of TGF-β from these tumor cells would inhibit tumor progression in vivo. Methods: TGF-β elimination was accomplished either by administration of neutralizing TGF-β antibody into mice receiving intravenous injection of Renca tumor cells or infection of TGF-β antisense expression vector into these tumor cells before subcutaneous injection into recipient mice. Results: Although a low dose of TGF-β antibody (5 mg/kg every 3 days) was without any effect, a high dose of TGF-β 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-β1 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-β1 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-β from the tumor cells. Our results also suggest that, although insensitive to TGF-β under in vitro conditions, Renca tumors could be inhibited by TGF-β removal through the systemic host environment.

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