TGF-β1 promotes motility and invasiveness of glioma cells through activation of ADAM17

The transforming growth factor 31 (TGF-beta 1) belongs to a family of structurally related polypeptide factors. TGF-beta plays an important role in the pathobiology of invasion of malignant gliomas. The objective of the present study was to investigate the impact of TNF-alpha converting enzyme (TACE/ADAM17) signaling on the process of TGF-beta 1-stimulated migration and invasion of T98G glioma cells. We found that TGF-beta 1 increased migration and invasiveness in glioma cells. Addition of the TGF-beta 1 receptor inhibitor, SB431542, reduced the TGF-beta 1-stimulated migration and invasiveness of glioma cells. In addition, TGF-beta 1-induced migration and invasiveness were also blocked by exposure to an ADAM 17 inhibitor, TAPI-2. Furthermore, ADAM 17 mRNA and protein expression were up-regulated by TGF-beta 1. Treatment with SB431542 and TAPI-2 blocked TGF-beta 1-induced ADAM 17 protein expression. In summary, these results indicate that TGF-beta 1 promotes cell migration and invasiveness of glioma cells through stimulation of ADAM17.