Increased expression of TGF-beta1 reduces tumor growth of human U-87 Glioblastoma Cells in vivo

• Published in: Cancer immunology, immunotherapy : CII immunotherapy : CII, 2006-08, Vol.55 (8), p.918-927
• Main Authors: Pan, Jen-Jung, Chang, Wei-Jen, Barone, Tara A, Plunkett, Robert J, Ostrow, Peter T, Greenberg, Steven J
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers, Tumor - analysis; Blotting, Northern; Blotting, Western; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; DNA Fragmentation; Glioblastoma - metabolism; Glioblastoma - pathology; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Rats; Rats, Nude; Receptors, Transforming Growth Factor beta - biosynthesis; Transduction, Genetic; Transforming Growth Factor beta1 - biosynthesis
• ISSN: 0340-7004

The role that transforming growth factor beta1 (TGF-beta1) plays in influencing growth of glioma cells is somewhat controversial. To further understand the potential growth-regulatory effects of TGF-beta1,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-beta1 and were highly tumorigenic. In contrast, U-87 cells transduced to express high levels of TGF-beta1 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-beta1 overproduction inhibited tumor growth through an autocrine mechanism, the highest TGF-beta1 producing cells were then double transduced with a vector expressing the kinase-truncated type II TGF-beta receptor. Cells expressing high levels of truncated TGF-beta receptor were less sensitive to TGF-beta1 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-beta1. These results also would tend to support the possibility that TGF-beta1 may be useful in treating some high-grade gliomas.