Increased expression of TGF-beta1 reduces tumor growth of human U-87 Glioblastoma Cells in vivo.
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.
Pan
Jen-Jung
JJ
Department of Neurology, Roswell Park Cancer Institute, Buffalo, NY, USA. panjenjung@hotmail.com
Chang
Wei-Jen
WJ
Barone
Tara A
TA
Plunkett
Robert J
RJ
Ostrow
Peter T
PT
Greenberg
Steven J
SJ
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D015152:Blotting, Northern; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051381:Rats; D011923:Rats, Nude; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis; D014161:Transduction, Genetic; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1