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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.

Rigogliuso S, Donati C, Cassarà D, Taverna S, Salamone M, Bruni P, Vittorelli ML - J Oncol (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Palermo, Viale delle, Scienze ed. 16, 90128 Palermo, Italy.

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.

No MeSH data available.


Related in: MedlinePlus

Comparative analysis of   β1 Integrin, SphK-2, and SphK-1 immunolocalization. (a) Localization in 8701-BC cells. (b) Localization in Sk-Hep1 cells. Line a: Immunolocalization of β1 Integrin and SphK-2 showing a different distribution of the two molecules. Line b: Immunolocalization of β1 Integrin and SphK-1. Arrows indicate colocalization areas.   β1 Integrin was detected using FITC-conjugated secondary antibodies and SphK-2 and SphK-1 using Texas red-conjugated secondary antibodies. Arrows indicate colocalization areas.
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fig1: Comparative analysis of   β1 Integrin, SphK-2, and SphK-1 immunolocalization. (a) Localization in 8701-BC cells. (b) Localization in Sk-Hep1 cells. Line a: Immunolocalization of β1 Integrin and SphK-2 showing a different distribution of the two molecules. Line b: Immunolocalization of β1 Integrin and SphK-1. Arrows indicate colocalization areas.   β1 Integrin was detected using FITC-conjugated secondary antibodies and SphK-2 and SphK-1 using Texas red-conjugated secondary antibodies. Arrows indicate colocalization areas.

Mentions: In a first group of experiments, expression and localization of SphK-1 and SphK-2 were analyzed by immunofluorescence in 8701 BC carcinoma cells and in Sk-Hep1 hepatocarcinoma cells (Figure 1).


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.

Rigogliuso S, Donati C, Cassarà D, Taverna S, Salamone M, Bruni P, Vittorelli ML - J Oncol (2010)

Comparative analysis of   β1 Integrin, SphK-2, and SphK-1 immunolocalization. (a) Localization in 8701-BC cells. (b) Localization in Sk-Hep1 cells. Line a: Immunolocalization of β1 Integrin and SphK-2 showing a different distribution of the two molecules. Line b: Immunolocalization of β1 Integrin and SphK-1. Arrows indicate colocalization areas.   β1 Integrin was detected using FITC-conjugated secondary antibodies and SphK-2 and SphK-1 using Texas red-conjugated secondary antibodies. Arrows indicate colocalization areas.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2875746&req=5

fig1: Comparative analysis of   β1 Integrin, SphK-2, and SphK-1 immunolocalization. (a) Localization in 8701-BC cells. (b) Localization in Sk-Hep1 cells. Line a: Immunolocalization of β1 Integrin and SphK-2 showing a different distribution of the two molecules. Line b: Immunolocalization of β1 Integrin and SphK-1. Arrows indicate colocalization areas.   β1 Integrin was detected using FITC-conjugated secondary antibodies and SphK-2 and SphK-1 using Texas red-conjugated secondary antibodies. Arrows indicate colocalization areas.
Mentions: In a first group of experiments, expression and localization of SphK-1 and SphK-2 were analyzed by immunofluorescence in 8701 BC carcinoma cells and in Sk-Hep1 hepatocarcinoma cells (Figure 1).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Palermo, Viale delle, Scienze ed. 16, 90128 Palermo, Italy.

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.

No MeSH data available.


Related in: MedlinePlus