Endothelial colony-forming cells (ECFCs), a unique endothelial stem cell population, are highly increased in the blood of Kaposi sarcoma (KS) patients. KS-derived ECFCs (KS-ECFCs) are also endowed with increased proliferative and vasculogenic potential, thus suggesting that they may be precursors of KS spindle cells. However, the mechanisms underlying the increased proliferative activity of KS-ECFCs remain poorly understood. Sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) are metabolically interconnected sphingoid mediators crucial to cell proliferation. Here, we investigated the metabolism, release, and proliferative effects of S1P and C1P in KS-ECFCs compared with control ECFCs (Ct-ECFCs). Metabolic studies by cell labeling, chromatographic analyses, and digital autoradiography revealed that S1P and C1P biosynthesis and S1P secretion are all efficient processes in KS-ECFCs, more efficient in KS-ECFCs than Ct-ECFCs. Quantitative PCR analyses demonstrated a significantly higher ceramide kinase and sphingosine kinase-2 expression in KS-ECFCs. Notably, also the expression of S1P1 and S1P3 receptors was augmented in KS-ECFCs. Accordingly, treatment with exogenous C1P or S1P induced a significant, concentration-dependent stimulation of KS-ECFC proliferation, but was almost completely ineffective in Ct-ECFCs. Hence, we identified C1P and S1P as autocrine/paracrine proliferative signals in KS-ECFCs. A better understanding of the mechanisms that enhance S1P/C1P formation in KS-ECFCs may yield effective therapeutic modalities.
Enhanced phosphorylation of sphingosine and ceramide sustains the exuberant proliferation of endothelial progenitors in Kaposi sarcoma / L. Abdel Hadi, F. Calcaterra, L. Brambilla, C. Carenza, G. Marfia, S. Della Bella, L. Riboni. - In: JOURNAL OF LEUKOCYTE BIOLOGY. - ISSN 0741-5400. - 103:3(2018), pp. 525-533.
|Titolo:||Enhanced phosphorylation of sphingosine and ceramide sustains the exuberant proliferation of endothelial progenitors in Kaposi sarcoma|
ABDEL HADI, LOUBNA (Co-primo)
CALCATERRA, FRANCESCA (Co-primo)
DELLA BELLA, SILVIA ANGELA MARIA (Penultimo)
RIBONI, LAURA PIERA CARLA GIULIA (Ultimo) (Corresponding)
|Parole Chiave:||Endothelial colony-forming cells; Kaposi sarcoma; ceramide-1-phosphate; sphingosine-1-phosphate|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
Settore MED/04 - Patologia Generale
|Data di pubblicazione:||2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/JLB.2MA0817-312R|
|Appare nelle tipologie:||01 - Articolo su periodico|