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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

  • Srivastava, Shilpee (Molecular Medicine Laboratory, Department of Biotechnology, Assam University) ;
  • Ghosh, Sankar Kumar (Molecular Medicine Laboratory, Department of Biotechnology, Assam University)
  • Published : 2015.11.04

Abstract

Background: 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. Materials and Methods: 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. Results: 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. 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.

Keywords

References

  1. Bhattacharjee A, Chakraborty A, Purkaystha P (2006). Prevalence of head and neck cancers in the north east - an institutional study. Indian J Otolaryngol Head Neck Surg, 58, 15-9.
  2. Bergeron C, Boulet LP, Page N, et al (2007). Influence of cigarette smoke on the arginine pathway in asthmatic airways: increased expression of arginase I. J Allergy Clin Immunol, 119, 391-7. https://doi.org/10.1016/j.jaci.2006.10.030
  3. Boffetta P, Hecht S, Gray N, et al (2008). Smokeless tobacco and cancer. Lancet Oncol, 9, 667-75. https://doi.org/10.1016/S1470-2045(08)70173-6
  4. Benz EJ Jr (2010). Learning about genomics and disease from the anucleate human red blood cell. J Clin Invest, 120, 4204-6. https://doi.org/10.1172/JCI45433
  5. Biczo G, Hegyi P, Berczi S, et al (2010). Inhibition of arginase activity ameliorates L-arginine-induced acute pancreatitis in rats. Pancreas, 39, 868-74. https://doi.org/10.1097/MPA.0b013e3181d371f8
  6. Buijs N, van Bokhorst-de van der Schueren MA, Langius JA, et al (2010). Perioperative arginine-supplemented nutrition in malnourished patients with head and neck cancer improves long-term survival. Am J Clin Nutr, 92, 1151-6. https://doi.org/10.3945/ajcn.2010.29532
  7. Barron L, Smith AM, El Kasmi KC, et al (2013). Role of arginase 1 from myeloid cells in th2-dominated lung inflammation. PLoS One, 8, 61961. https://doi.org/10.1371/journal.pone.0061961
  8. Chang CI, Liao JC, Kuo L (1998). Arginase modulates nitric oxide production in activated macrophages. Am J Physiol, 274, 342-8
  9. Choudhury B, Srivastava S, Choudhury HH, et al (2014). Arginase and C-reactive protein as potential serum-based biomarker of head and neck squamous cell carcinoma patients of north east India. Tumor Biol, 35, 6739-48. https://doi.org/10.1007/s13277-014-1851-y
  10. Das P, Lahiri A, Chakravortty D (2010). Modulation of the arginase pathway in the context of microbial pathogenesis: a metabolic enzyme moonlighting as an immune modulator. PLoS Pathog, 6, 1000899. https://doi.org/10.1371/journal.ppat.1000899
  11. Dal Maso L, Torelli N, Biancotto E, et al (2015). Combined effect of tobacco smoking and alcohol drinking in the risk of head and neck cancers: a re-analysis of case-control studies using bi-dimensional spline models. Eur J Epidemiol, [Epub ahead of print]
  12. Erber WN, Pinching AJ, Mason DY, (1984). Immunohistochemical detection of T and B cell populations in routine blood smears. Lancet, 323, 1042-6. https://doi.org/10.1016/S0140-6736(84)91451-X
  13. Gilmour SK, Verma AK, Madara T, et al (1987). Regulation of ornithine decarboxylase gene expression in mouse epidermis and epidermal tumors during two-stage tumorigenesis. Cancer Res, 47, 1221-5.
  14. Gijare PS, Rao KVK, Bhide SV, (1989). Effects of tobaccospecific nitrosamines and snuff extract on cell proliferation and activities of ornithine decarboxylase and aryl hydrocarbon hydroxylase in mouse tongue primary epithelial cell cultures. J Can Res Clin Oncol, 115, 558-63. https://doi.org/10.1007/BF00391358
  15. Gourin CG, Podolsky RH, (2006). Racial disparities in patients with head and neck squamous cell carcinoma. Laryngoscope, 116, 1093-106. https://doi.org/10.1097/01.mlg.0000224939.61503.83
  16. Garcia V, Garcia JM, Pena C, et al (2008). Free circulating mRNA in plasma from breast cancer patients and clinical outcome. Cancer Lett, 263, 312-20. https://doi.org/10.1016/j.canlet.2008.01.008
  17. Grabon W, Mielczarek-Puta M, Chrzanowska A, et al (2009). L-arginine as a factor increasing arginase significance in diagnosis of primary and metastatic colorectal cancer. Clin Biochem, 42, 353-7. https://doi.org/10.1016/j.clinbiochem.2008.11.018
  18. Haenisch B, von Kugelgen I, Bonisch H, et al (2008). Regulatory mechanisms underlying agmatine homeostasis in humans. Am J Physiol Gastrointest Liver Physiol, 295, 1104-10 https://doi.org/10.1152/ajpgi.90374.2008
  19. Hashibe M, Brennan P, Chuang SC, et al (2009) Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Can Epidem Biomark Prev, 18, 541-50. https://doi.org/10.1158/1055-9965.EPI-08-0347
  20. Hauswald H, Simon C, Hecht S, et al (2011). Long-term outcome and patterns of failure in patients with advanced head and neck cancer. Radiat Oncol, 6, 70. https://doi.org/10.1186/1748-717X-6-70
  21. Jacobsen LC, Theilgaard-Monch K, Christensen EI, et al (2007). Arginase 1 is expressed in myelocytes/metamyelocytes and localized in gelatinase granules of human neutrophils. Blood, 109, 3084-7.
  22. Kitowska K, Zakrzewicz D, Konigshoff M, et al (2008). Functional role and species-specific contribution of arginases in pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol, 294, 34-45. https://doi.org/10.1152/ajplung.00007.2007
  23. Kim J, Shin JM, Jeon YJ, et al (2012). Proteomic validation of multifunctional molecules in mesenchymal stem cells derived from human bone marrow, umbilical cord blood and peripheral blood. PLoS One, 7, 32350. https://doi.org/10.1371/journal.pone.0032350
  24. Love RR, Astrow SH, Cheeks AM, et al (2003). Ornithine decarboxylase (ODC) as a prognostic factor in operable breast cancer. Breast Cancer Res Treat, 79, 329-34. https://doi.org/10.1023/A:1024014508016
  25. Lopez V, Alarcon R, Orellana MS, et al (2005). Insights into the interaction of human arginase II with substrate and manganese ions by site-directed mutagenesis and kinetic studies. Alteration of substrate specificity by replacement of Asn149 with Asp. Febs J, 272, 4540-8. https://doi.org/10.1111/j.1742-4658.2005.04874.x
  26. Matthaei KI, Williams JF (1987). Ornithine aminotransferase turnover in host tissues of tumor-bearing rats. J Nat Can Inst, 79, 805-9.
  27. Molnar B, Ladanyi A, Tanko L, et al (2001). Circulating tumor cell clusters in the peripheral blood of colorectal cancer patients. Clin Can Res, 7, 4080-5.
  28. Munder M, Mollinedo F, Calafat J, et al (2005). Arginase I is constitutively expressed in human granulocytes and participates in fungicidal activity. Blood, 105, 2549-56. https://doi.org/10.1182/blood-2004-07-2521
  29. Mondal R, Ghosh SK, Choudhury JH, et al (2013). Mitochondrial DNA copy number and risk of oral cancer: a report from Northeast India. PLoS One, 8, 57771. https://doi.org/10.1371/journal.pone.0057771
  30. Mussai F1, De Santo C, Abu-Dayyeh I, et al (2013). Acute myeloid leukemia creates an arginase-dependent immunosuppressive microenvironment. Blood, 122, 749-58. https://doi.org/10.1182/blood-2013-01-480129
  31. Mohammed A, Janakiram NB, Madka V, et al (2014). Eflornithine (DFMO) prevents progression of pancreatic cancer by modulating ornithine decarboxylase signaling. Cancer Prev Res (Phila), 7, 1198-209. https://doi.org/10.1158/1940-6207.CAPR-14-0176
  32. O'Brian TG, Megosh LC, et al (1997). Ornithine decarboxylase over expression is a sufficient condition for tumor promotion in mouse skin. Cancer Res, 57, 2630-7.
  33. Polat MF, Taysİ S, Polat S, et al (2003). Elevated serum arginase activity levels in patients with breast cancer. Surg Today, 33, 655-61. https://doi.org/10.1007/s00595-002-2563-2
  34. Rodriguez PC, Ernstoff MS, Hernandez C, et al (2009). Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Can Res, 69, 1553-60. https://doi.org/10.1158/0008-5472.CAN-08-1921
  35. Ramirez-Zamora S, Mendez-Rodriguez ML, Olguin-Martinez M, et al (2013). Increased erythrocytes by-products of arginine catabolism are associated with hyperglycemia and could be involved in the pathogenesis of type 2 diabetes mellitus. PLoS One, 8, 66823. https://doi.org/10.1371/journal.pone.0066823
  36. Stabellini G, Calastrini C, Gagliano N, et al (2003). Polyamine levels and ornithine decarboxylase activity in blood and erythrocytes in human diseases. Int J Clin Pharmacol Res, 23, 17-22.
  37. Skorupski KA, O'Brien TG, Guerrero T, et al (2011). Phase I/II clinical trial of 2-difluoromethyl-ornithine (DFMO) and a novel polyamine transport inhibitor (MQT 1426) for feline oral squamous cell carcinoma. Vet Comp Oncol, 9, 275-82. https://doi.org/10.1111/j.1476-5829.2011.00264.x
  38. Vilas-Boas W, Cerqueira BA, Zanette AM, et al (2010). Arginase levels and their association with Th17-related cytokines, soluble adhesion molecules (sICAM-1 and sVCAM-1) and hemolysis markers among steady-state sickle cell anemia patients. Ann Hematol, 89, 877-82. https://doi.org/10.1007/s00277-010-0954-9
  39. Wolf C, Bruss M, Hanisch B, et al (2007). Molecular basis for the antiproliferative effect of agmatine in tumor cells of colonic, hepatic, and neuronal origin. Mol Pharmacol, 71, 276-83
  40. Yamamoto Y, Sousse LE, Enkhbaatar P, et al (2012). Gammatocopherol nebulization decreases oxidative stress, arginase activity, and collagen deposition after burn and smoke inhalation in the ovine model. Shock, 38, 671-6.
  41. Yang J, Gonon AT, Sjoquist PO, et al (2013). Arginase regulates red blood cell nitric oxide synthase and export of cardioprotective nitric oxide bioactivity. Proc Natl Acad Sci, 110, 15049-54. https://doi.org/10.1073/pnas.1307058110