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.
OBJECTIVES: The mouserenal 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: Maite Alvarez; Myriam N Bouchlaka; Gail D Sckisel; Can M Sungur; Mingyi Chen; William J Murphy Journal: J Immunol Date: 2014-07-07 Impact factor: 5.422
Authors: Qiang Zhang; Lin Chen; Brian T Helfand; Thomas L Jang; Vidit Sharma; James Kozlowski; Timothy Michael Kuzel; Lihua J Zhu; Ximing J Yang; Borko Javonovic; Yinglu Guo; Scott Lonning; Jay Harper; Beverly A Teicher; Charles Brendler; Nengwang Yu; William J Catalona; Chung Lee Journal: PLoS One Date: 2011-09-30 Impact factor: 3.240