title: TGF-β1 promotes motility and invasiveness of glioma cells through activation of ADAM17.
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.
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lu
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.forename: Xuguang
authors.initials: X
authors.lastname: Zheng
authors.forename: Mark
authors.initials: M
authors.lastname: Katakowski
authors.forename: Benjamin
authors.initials: B
authors.lastname: Buller
authors.forename: Shing-Shun Tony
authors.initials: SS
authors.lastname: To
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072198:ADAM17 Protein; D001549:Benzamides / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004149:Dioxoles / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human