An Active Formof Sphingosine Kinase-1 Is Released inthe ExtracellularMedium as Component ofMembrane VesiclesShed by Two Human Tumor Cell Lines

Salvatrice Rigogliuso, Simona Taverna, Monica Salamone, Chiara Donati, Paola Bruni, Maria Letizia Vittorelli, Monica Salamone

Risultato della ricerca: Articlepeer review

21 Citazioni (Scopus)

Abstract

Expression of sphingosine kinase-1 (SphK-1) correlates with poor survival of tumor patients. Thiseffect is probably due to the capability of SphK-1 to be released into the extracellular mediumwhere it catalyzes the biosynthesis of sphingosine 1-phosphate (S1P), a signalling moleculeendowed with profound proangiogenic effects. SphK-1 is a leader-less protein and it is secreted byunconventional mechanism. We report that in human hepatocarcinoma Sk-Hep1 cells, targeting ofthe enzyme to the cell surface is induced by extracellular signalling and parallels targeting of FGF-2to the budding vesicles. We also show that SphK-1 is present in a catalitycally active form invesicles shed by SK-Hep1 and human breast carcinoma 8701-BC cells. The enzyme substratesphingosine is present in shed vesicles where it is produced by neutral ceramidase. Shed vesicles aretherefore a site for S1P production in the extracellular medium, and conceivably also within hostcell, after vesicle endocytosis.
Lingua originaleEnglish
pagine (da-a)1-10
Numero di pagine10
RivistaJournal of Oncology
Volume2010
Stato di pubblicazionePublished - 2010

All Science Journal Classification (ASJC) codes

  • Oncology

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