Artikel
Expression of active Transforming-growth factor beta in glioblastomas – TGF-beta as a possible therapeutic target
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Veröffentlicht: | 8. Juni 2016 |
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Gliederung
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Objective: Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory cytokine that has pleiotropic functions, regulating cell differentiation, proliferation, angiogenesis and immune function. Furthermore, a large body of evidence suggests that TGF-beta has profound effects on tumour biology. These partial contrary functions indicate a context-dependent and cell-specific function of the molecule and show that a well regulated and controlled expression of this cytokine is of outmost importance. TGF-beta is secreted as a latent complex and is activated in vivo by certain mechanisms involving proteases. Only the active form is able to bind the TGF-beta receptors and transduce a signal in the cascade. The activation of these latent forms represents a crucial step in the regulation of TGF-beta-activity. The aim of this study is to analyse the expression of the active form of TGF-beta in glioblastomas.
Method: Active TGF-beta in fresh-frozen glioblastoma tissue was determined using the plasminogen activator inhibitor-I promoter luciferase (PAI/L) assay. For the PAI/L assay, a truncated TGF-beta-inducible PAI-1 promoter was fused to a firefly luciferase reporter gene and subsequently transfected into mink lung epithelial cells (MLECs) generating a highly sensitive TGF-beta-responsive cell line. Appropriate cell lines were analysed.
Results: Active TGF-beta was expressed by glioblastomas in high concentrations. Nine glioblastoma samples were analysed. The medium expression of active TGF-beta was 97.1 pg/mm3 ranging from 10.3 to 377.4 pg/mm3. U87 glioblastoma cells had a medium expression of active TGF-beta of 5.4 pg/mm3 and normal astrocytic cells of 3.3 pg/mm3. These data show that the tumour microenvironment plays an important role in the activation of TGF-beta as active TGF-beta is significantly higher expressed in glioblastoma tissue than in appropriate cell lines.
Conclusions: These findings are consistent with current literature and indicate that TGF-beta plays an important role in the generation of a tumour-supporting microenvironment and contributes to glioblastoma development. These data suggest TGF-beta as a possible therapeutic target in the therapy of glioblastomas.