Cathepsin B Modulation of Urokinase-type Plasminogen Activator and Ovarian Cancer Cell Invasion by in Vitro

نویسندگان

  • Hiroshi Kobayashi
  • Hidekazu Ohi
  • Motoi Sugimura
  • Hiromitsu Shinohara
  • Toshiro Fuji
  • Toshihiko Terao
چکیده

HOC-I ovarian cancer cells express the single-chain form of the urokinase-type plasminogen activator (uPA) and cathepsin B (calli B) on their cell surface. The significance of the expression of cell surface uPA/ cath B activity to the invasive potential was examined by preincubating with uPA/cath B-modulating agents in in vitro invasion assay. The antiuPA monoclonal antibody 394 effectively inhibited invasion in a dosedependent manner. On the contrary, anti-cath B antibody did not affect the invasive potential of the cells. 1-6-1. a specific inhibitor for cysteine proteases, blocked invasion as effectively as monoclonal antibody 394. The data reveal that the uPA and cysteine proteases contribute signifi cantly to the invasive capacity of the cells. We suggest that the cysteine proteases facilitate the action of uPA, possibly by activating proenzyme uPA produced by cancer cells. Evidence for the role of a cathepsin-uPA activation cascade in HOC-I cell invasion is provided.

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تاریخ انتشار 2006