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.
Rigogliuso, S., Donati, C., Cassarà, D., Taverna, S., Salamone, M., Bruni, P., et al. (2010). An Active Formof Sphingosine Kinase-1 Is Released in the ExtracellularMedium as Component ofMembrane Vesicles Shed by Two Human Tumor Cell Lines. JOURNAL OF ONCOLOGY, 2010(Volume 2010, Article ID 509329,), 1-10 [10.1155/2010/509329].
An Active Formof Sphingosine Kinase-1 Is Released in the ExtracellularMedium as Component ofMembrane Vesicles Shed by Two Human Tumor Cell Lines
RIGOGLIUSO, Salvatrice;TAVERNA, Simona;SALAMONE, Monica;VITTORELLI, Maria Letizia
2010-01-01
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.
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