Abstract
Arginine may play important roles in tumor progression by providing ornithine for polyamine biosynthesis, required for cell growth. The aim of this work was to determine the expression of arginine metabolic pathway enzymes in head and neck squamous cell carcinoma (HNSCC) in northeast India. 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 by immunohistochemistry. Immunocytochemistry, semiquantitative reverse transcription sq-PCR and quantitative real-time qPCR were used to assess protein and mRNA expressions in peripheral blood of fifty HNSCC patients and hundred controls. ARG1 and ODC protein and mRNA were strongly expressed in peripheral blood from HNSCC patients. No ARG2 expression was observed. In vivo, expression of ARG1, ARG2 and ODC was significantly higher in tumor than in non-tumor tissues. Most tumors expressed low levels of OAT, with no difference in tissues or blood, compared to controls. The absolute extent of maximal ARG1 upregulation with qPCR showed 6.23 fold increase in HNSCC. These findings strongly suggest that in HNSCCs, the ARG1 pathway is stimulated leading to the formation of polyamines as indicated by higher ODC expression, which promote tumor growth.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer worldwide and is the most common neoplasm in central Asia (Hashibe et al, 2009)
The aim of this work was to determine the expression of arginine metabolic pathway enzymes in head and neck squamous cell carcinoma (HNSCC) in northeast India
ARG1 and ornithine decarboxylase (ODC) protein and mRNA were strongly expressed in peripheral blood from HNSCC patients
Summary
Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer worldwide and is the most common neoplasm in central Asia (Hashibe et al, 2009). Early-stage HNSCC has high cure rates, up to 50% of patients present in advanced disease (Gourin and Podolsky, 2006). In India, the HNSCC accounts for 30-40% cancers at all sites It is the sixth most common cause of death in males and seventh in females. The aim of this work was to determine the expression of arginine metabolic pathway enzymes in head and neck squamous cell carcinoma (HNSCC) in northeast India. Results: ARG1 and ODC protein and mRNA were strongly expressed in peripheral blood from HNSCC patients. Conclusions: These findings strongly suggest that in HNSCCs, the ARG1 pathway is stimulated leading to the formation of polyamines as indicated by higher ODC expression, which promote tumor growth
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