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SALVATRICE RIGOGLIUSO

An Active Formof Sphingosine Kinase-1 Is Released in the ExtracellularMedium as Component ofMembrane Vesicles Shed by Two Human Tumor Cell Lines

  • Autori: Rigogliuso, S; Donati,C; Cassarà,D; Taverna,S; Salamone,M; Bruni,P; Vittorelli,ML;
  • Anno di pubblicazione: 2010
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • Parole Chiave: membrane vesicles
  • OA Link: http://hdl.handle.net/10447/56313

Abstract

Expression of sphingosine kinase-1 (SphK-1) correlates with poor survival of tumor patients. This effect is probably due to the capability of SphK-1 to be released into the extracellular medium where it catalyzes the biosynthesis of sphingosine 1-phosphate (S1P), a signalling molecule endowed with profound proangiogenic effects. SphK-1 is a leader-less protein and it is secreted by unconventional mechanism. We report that in human hepatocarcinoma Sk-Hep1 cells, targeting of the enzyme to the cell surface is induced by extracellular signalling and parallels targeting of FGF-2 to the budding vesicles. We also show that SphK-1 is present in a catalitycally active form in vesicles shed by SK-Hep1 and human breast carcinoma 8701-BC cells. The enzyme substrate sphingosine is present in shed vesicles where it is produced by neutral ceramidase. Shed vesicles are therefore a site for S1P production in the extracellular medium, and conceivably also within host cell, after vesicle endocytosis.