Inhibition of ADAM17 reduces hypoxia-induced brain tumor cell invasiveness

摘要: The membrane-anchored metalloproteinase tumor necrosis factor-alpha-converting enzyme (TACE/a disintegrin and [ADAM] 17) is key in proteolytic ectodomain shedding of several membrane-bound growth factors, cytokines receptors. expression activity ADAM17 increases under some pathological conditions including stroke, promotes neural progenitor cell migration contributes to stroke-induced neurogenesis. Hypoxia initiates cellular invasive processes that occur both physiological such as invasion metastasis tumors. In the present study, we sought elucidate whether brain invasion. To this end, examined role invasiveness two different lines, 9L rat gliosarcoma U87 human glioma, normoxic hypoxic conditions. Additionally, tested effects suppression on vitro by means inhibitors specific small interfering RNA. We found cells upregulated hypoxia, correlated with increased Conversely, proteolysis decreased induced hypoxia cells. Furthermore, contribution was independent matrix (MMP)-2 MMP-9 activity. also activate epidermal factor/phosphoinositide-3 kinase/serine/threonine kinase signal transduction pathway. Our data suggest hypoxia-induced glioma through activation EGFR