TY - JOUR
T1 - Treatment of Transforming Growth Factor-Beta-Insensitive Mouse Renca Tumor by Transforming Growth Factor-Beta Elimination
AU - Perry, Kent
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
N1 - Funding Information:
C. Lee is a study investigator partially funded by Genzyme Corporation.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/7
Y1 - 2008/7
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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U2 - 10.1016/j.urology.2007.11.091
DO - 10.1016/j.urology.2007.11.091
M3 - Article
C2 - 18295867
AN - SCOPUS:45849090359
SN - 0090-4295
VL - 72
SP - 225
EP - 229
JO - Urology
JF - Urology
IS - 1
ER -