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Journal of Oncology
Volume 2010 (2010), Article ID 509329, 10 pages
http://dx.doi.org/10.1155/2010/509329
Research Article

An Active Form of Sphingosine Kinase-1 Is Released in the Extracellular Medium as Component of Membrane Vesicles Shed by Two Human Tumor Cell Lines

1Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Palermo, Viale delle, Scienze ed. 16, 90128 Palermo, Italy
2Dipartimento di Scienze Biochimiche, Università di Firenze, Viale G.B. Morgagni n. 50, 50134 Florence, Italy
3Dipartimento Biopatologia e Metodologie Biomediche, Università di Palermo, Via Divisi 83, 90133 Palermo, Italy
4IAMC-CNR, U.O. Capo Granitola, Mazara del Vallo, 91026 Trapani, Italy

Received 16 November 2009; Accepted 8 March 2010

Academic Editor: Kalpna Gupta

Copyright © 2010 Salvatrice Rigogliuso et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Expression of sphingosine kinase-1 (SphK-1) correlates with a poor survival rate of tumor patients. This effect is probably due to the ability of SphK-1 to be released into the extracellular medium where it catalyzes the biosynthesis of sphingosine-1-phosphate (S1P), a signaling molecule endowed with profound proangiogenic effects. SphK-1 is a leaderless protein which is secreted by an unconventional mechanism. In this paper, we will show that in human hepatocarcinoma Sk-Hep1 cells, extracellular signaling is followed by targeting the enzyme to the cell surface and parallels targeting of FGF-2 to the budding vesicles. We will 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 following vesicle endocytosis.