Transforming growth factor-β pathway activity in glioblastoma

被引：78
|
作者：
Frei, Karl [1 ]
Gramatzki, Dorothee [2 ]
Tritschler, Isabel [2 ]
Schroeder, Judith Johanna [2 ]
Espinoza, Larisa [1 ]
Rushing, Elisabeth Jane [3 ]
Weller, Michael [2 ,4 ]
机构：
[1] Univ Zurich Hosp, Dept Neurosurg, CH-8091 Zurich, Switzerland
[2] Univ Zurich Hosp, Dept Neurol, Lab Mol Neurooncol, CH-8091 Zurich, Switzerland
[3] Univ Zurich Hosp, Dept Neuropathol, CH-8091 Zurich, Switzerland
[4] Univ Zurich, Neurosci Ctr Zurich, Zurich, Switzerland
来源：
ONCOTARGET | 2015年 / 6卷 / 08期
关键词：
TGF-beta; PDGF-B; PAI-1; glioblastoma; biomarker; GLIOMA; TRABEDERSEN; ACTIVATION; MECHANISMS;
D O I：
10.18632/oncotarget.3467
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Transforming growth factor (TGF)-beta is a central molecule maintaining the malignant phenotype of glioblastoma. Anti-TGF-beta strategies are currently being explored in early clinical trials. Yet, there is little contemporary data on the differential expression of TGF-beta isoforms at the mRNA and protein level or TGF-beta/Smad pathway activity in glioblastomas in vivo. Here we studied 64 newly diagnosed and 16 recurrent glioblastomas for the expression of TGF-beta 1-3, platelet-derived growth factor (PDGF)-B, and plasminogen activator inhibitor (PAI)-1 mRNA by RT-PCR and for the levels of TGF-beta 1-3 protein, phosphorylated Smad2 (pSmad2), pSmad1/5/8 and PAI-1 by immunohistochemistry. Among the TGF-beta isoforms, TGF-beta 1 mRNA was the most, whereas TGF-beta 3 mRNA was the least abundant. TGF-beta 1-3 mRNA expression was strongly correlated, as was the expression of TGF-beta 1-3 mRNA, and of the TGF-beta 1-3 target genes, PDGF-B and PAI1. TGF-beta 2 and TGF-beta 3 protein levels correlated well, whereas the comparison of the other TGF-beta isoforms did not. Positive correlation was also observed between TGF-beta 1 and pSmad1/5/8 and between pSmad2 and pSmad1/5/8. Survival analyses indicated that a group of patients with high expression levels of TGF-beta 2 mRNA or pSmad1/5/8 protein have inferior outcome. We thus provide potential biomarkers for patient stratification in clinical trials of anti-TGF-beta therapies in glioblastoma.
引用
收藏
页码：5963 / 5977
页数：15
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