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

Oncol Rep. 2011 May;25(5):1329-35. doi: 10.3892/or.2011.1195. Epub 2011 Feb 24.

Abstract

The transforming growth factor β1 (TGF-β1) 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-α converting enzyme (TACE/ADAM17) signaling on the process of TGF-β1-stimulated migration and invasion of T98G glioma cells. We found that TGF-β1 increased migration and invasiveness in glioma cells. Addition of the TGF-β1 receptor inhibitor, SB431542, reduced the TGF-β1-stimulated migration and invasiveness of glioma cells. In addition, TGF-β1-induced migration and invasiveness were also blocked by exposure to an ADAM17 inhibitor, TAPI-2. Furthermore, ADAM17 mRNA and protein expression were up-regulated by TGF-β1. Treatment with SB431542 and TAPI-2 blocked TGF-β1-induced ADAM17 protein expression. In summary, these results indicate that TGF-β1 promotes cell migration and invasiveness of glioma cells through stimulation of ADAM17.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism*
  • ADAM17 Protein
  • Benzamides / pharmacology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Dioxoles / pharmacology
  • Enzyme Activation / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / genetics
  • Glioma / metabolism*
  • Humans
  • Neoplasm Invasiveness
  • RNA, Messenger / genetics
  • Signal Transduction / drug effects
  • Transforming Growth Factor beta1 / antagonists & inhibitors
  • Transforming Growth Factor beta1 / metabolism
  • Transforming Growth Factor beta1 / pharmacology*

Substances

  • 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
  • Benzamides
  • Dioxoles
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • ADAM Proteins
  • ADAM17 Protein
  • ADAM17 protein, human