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 language | English (US) |
|---|---|
| Pages (from-to) | 225-229 |
| Number of pages | 5 |
| Journal | Urology |
| Volume | 72 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 1 2008 |
Fingerprint
ASJC Scopus subject areas
- Urology
Cite this
}
Treatment of Transforming Growth Factor-Beta-Insensitive Mouse Renca Tumor by Transforming Growth Factor-Beta Elimination. / Perry, Kent; 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 journal › Article
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
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.
UR - http://www.scopus.com/inward/record.url?scp=45849090359&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=45849090359&partnerID=8YFLogxK
U2 - 10.1016/j.urology.2007.11.091
DO - 10.1016/j.urology.2007.11.091
M3 - Article
C2 - 18295867
AN - SCOPUS:45849090359
VL - 72
SP - 225
EP - 229
JO - Urology
JF - Urology
SN - 0090-4295
IS - 1
ER -