Modulation of L-Arginine-Arginase Metabolic Pathway Enzymes: Immunocytochemistry and mRNA Expression in Peripheral Blood and Tissue Levels in Head and Neck Squamous Cell Carcinomas in North East India

Abstract

<b>Background:</b> Arginine may play important roles in tumor progression by providing ornithine for polyaminebiosynthesis, required for cell growth. The aim of this work was to determine the expression of argininemetabolic pathway enzymes in head and neck squamous cell carcinoma (HNSCC) in northeast India. Materialsand <br/><b>Methods</b>: The expressions of arginase isoforms (ARG1 and ARG2), ornithine aminotransferase (OAT)and ornithine decarboxylase (ODC) were examined in fifty paired HNSCC and adjacent non-tumor tissues byimmunohistochemistry. Immunocytochemistry, semiquantitative reverse transcription sq-PCR and quantitativereal-time qPCR were used to assess protein and mRNA expressions in peripheral blood of fifty HNSCC patientsand hundred controls. <br/><b>Results</b>: ARG1 and ODC protein and mRNA were strongly expressed in peripheralblood from HNSCC patients. No ARG2 expression was observed. In vivo, expression of ARG1, ARG2 and ODCwas significantly higher in tumor than in non-tumor tissues. Most tumors expressed low levels of OAT, with nodifference in tissues or blood, compared to controls. The absolute extent of maximal ARG1 upregulation withqPCR showed 6.23 fold increase in HNSCC. <br/><b>Conclusions</b>: These findings strongly suggest that in HNSCCs, theARG1 pathway is stimulated leading to the formation of polyamines as indicated by higher ODC expression,which promote tumor growth