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- Title
Increased expression of TGF-β1 reduces tumor growth of human U-87 Glioblastoma Cells in vivo.
- Authors
Jen-Jung Pan; Wei-Jen Chang; Barone, Tara A.; Plunkett, Robert J.; Ostrow, Peter T.; Greenberg, Steven J.
- Abstract
The role that transforming growth factor β1 (TGF-β1) plays in influencing growth of glioma cells is somewhat controversial. To further understand the potential growth-regulatory effects of TGF-β1,we constructed an animal astroglial tumor model by injecting either wild-type or virally transduced human U-87 glioblastoma cells into nude rat brains. Wild type U-87 cells produced very low amounts of TGF-β1 and were highly tumorigenic. In contrast, U-87 cells transduced to express high levels of TGF-β1 showed reduced tumor size in vivo, in a dose-dependent manner. This reduction in tumor size was not due to either decreased vascularity or increased apoptosis. To test whether TGF-β1 overproduction inhibited tumor growth through an autocrine mechanism, the highest TGF-β1 producing cells were then double transduced with a vector expressing the kinase-truncated type II TGF-β receptor. Cells expressing high levels of truncated TGF-β receptor were less sensitive to TGF-β1 mediated growth inhibition in vitro and produced more aggressive tumors in vivo. The data suggest that the degree of tumorigenicity of the U-87 high-grade glioblastoma cell line may be associated with correspondingly low level of production of TGF-β1. These results also would tend to support the possibility that TGF-β1 may be useful in treating some high-grade gliomas.
- Subjects
TRANSFORMING growth factors-beta; GLIOMAS; TUMOR growth; TUMORS; TRANSFORMING growth factors
- Publication
Cancer Immunology, Immunotherapy, 2006, Vol 55, Issue 8, p918
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-005-0083-9