Transforming growth factor-? pathway activity in glioblastoma
#MMPMID25849941
Frei K
; Gramatzki D
; Tritschler I
; Schroeder JJ
; Espinoza L
; Rushing EJ
; Weller M
Oncotarget
2015[Mar]; 6
(8
): 5963-77
PMID25849941
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Transforming growth factor (TGF)-? is a central molecule maintaining the
malignant phenotype of glioblastoma. Anti-TGF-? strategies are currently being
explored in early clinical trials. Yet, there is little contemporary data on the
differential expression of TGF-? isoforms at the mRNA and protein level or
TGF-?/Smad pathway activity in glioblastomas in vivo.Here we studied 64 newly
diagnosed and 16 recurrent glioblastomas for the expression of TGF-?1-3,
platelet-derived growth factor (PDGF)-B, and plasminogen activator inhibitor
(PAI)-1 mRNA by RT-PCR and for the levels of TGF-?1-3 protein, phosphorylated
Smad2 (pSmad2), pSmad1/5/8 and PAI-1 by immunohistochemistry.Among the TGF-?
isoforms, TGF-?1 mRNA was the most, whereas TGF-?3 mRNA was the least abundant.
TGF-?1-3 mRNA expression was strongly correlated, as was the expression of
TGF-?1-3 mRNA, and of the TGF-?1-3 target genes, PDGF-B and PAI-1. TGF-?2 and
TGF-?3 protein levels correlated well, whereas the comparison of the other
TGF-?isoforms did not. Positive correlation was also observed between TGF-?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-?2 mRNA or pSmad1/5/8
protein have inferior outcome.We thus provide potential biomarkers for patient
stratification in clinical trials of anti-TGF-? therapies in glioblastoma.
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