PO-262 Differential expression of Sphingosine-1-Phosphate metabolising enzymes in oral squamous cell carcinoma

Abstract

IntroductionSphingosine-1-phosphate (S1P), a potent signalling lipid. It mediates its actions by binding to a family of G-protein coupled receptors (GPCRs), known as S1P receptors. It has been implicated in the several processes integral to carcinogenesis. S1P signalling promotes cancer by inhibiting apoptosis and by enhancing proliferation, transformation, angiogenesis and inflammation. S1P levels are regulated by eight enzymes i.e. sphingosine kinases (SphK1 and SphK2), five lipid phosphatases and a S1P lyase. The role of S1P metabolising enzymes in oral squamous cell carcinoma (OSCC) has not been fully understood.Material and methodsHere, we determined the mRNA expression profile of eight S1P metabolising genes (SphK1, SphK2, SGPL1, SGPP1, SGPP2, LPP1, LPP2 and LPP3) quantitative real-time PCR in tumour tissues of 50 OSCC patients compared with adjacent normal tissue of the same patient. We also performed immunohistochemistry for Sphk1, SphK2, SGPP1 and LPP3 in the paraffin-embedded sections of tumour tissues of OSCC patients and normal mucosa.Results and discussionsIn this study, we demonstrate that the expression of four out of eight major enzymes that regulate S1P levels were altered significantly in OSCC. Expression levels of SphK1 and SGPP1 genes were upregulated significantly in 70% and 75% OSCC tumours, respectively. Importantly, expression levels of SphK2 and LPP3 (PPAB2B) were downregulated in tumour tissue of 70% of OSCC patients. Cytoplasmic positivity for SphK1 was observed in majority of tumour cases in malignant squamous epithelial cells. Most of these cases showed high positivity. However, low IRS score was observed SphK2 in the tumours. Amongst the non-epithelial tissues, cytoplasmic positivity was also noted for SphK1 and SphK2 in the skeletal muscle fibres.ConclusionOur data shows that S1P metabolising enzymes are expressed differentially in OSCC tumours, further studies are warranted to determine their role in carcinogenesis of OSCC.