Participation of Thrombospondin-1 in the Activation of Latent Transforming Growth Factor-.BETA. in Malignant Glioma Cells.

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Abstract
Malignant glioma cells secrete transforming growth factor-β (TGF-β) and can activate latent TGF-β. However, the mechanism of the latent TGF-β activation has not yet been determined. This study examined whether thrombospondin-1 (TSP-1) secreted by malignant glioma cell lines participates in the activation of latent TGF-β secreted by the glioma cells. Western blot analysis revealed that TSP-1 was present in both the cell lysates and the culture supernatants of all three malignant glioma cell lines (T98G, A172, and U251). A bioassay for TGF-β activity revealed that all malignant glioma cell lines used in this study could activate latent TGF-β by themselves. Latent TGF-β1 activation, evaluated by enzyme-linked immunosorbent assay, was inhibited by more than 50% by the addition of neutralizing anti-TSP-1 monoclonal antibody or anti-TSP-1 polyclonal antibody. These results indicate that TSP-1 has a predominant role in the activation of latent TGF-β in malignant glioma cells.