eISSN: 1897-4317
ISSN: 1895-5770
Gastroenterology Review/Przegląd Gastroenterologiczny
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4/2016
vol. 11
 
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abstract:
Original paper

Immunohistochemical assessment of mitochondrial superoxide dismutase (MnSOD) in colorectal premalignant and malignant lesions

Adam Piecuch, Marlena Brzozowa-Zasada, Bartosz Dziewit, Oliwia Segiet, Józef Kurek, Grażyna Kowalczyk-Ziomek, Romuald Wojnicz, Krzysztof Helewski

Gastroenterology Rev 2016; 11 (4): 239–246
Online publish date: 2016/02/16
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Introduction: It is generally accepted that mitochondria are a primary source of intracellular reactive oxygen species (ROS). Under physiological circumstances they are permanently formed as by-products of aerobic metabolism in the mitochondria. To counter the harmful effect of ROS, cells possess an antioxidant defence system to detoxify ROS and avert them from accumulation at high concentrations. Mitochondria-located manganese superoxide dismutase (MnSOD, SOD2) successfully converts superoxide to the less reactive hydrogen peroxide (H2O2). To the best of our knowledge, there are no available data regarding immunohistochemical expression of MnSOD in colorectal neoplastic tissues.

Aim: To investigate the immunohistochemical expression status of MnSOD in colorectal premalignant and malignant lesions.

Material and methods: This study was performed on resected specimens obtained from 126 patients who had undergone surgical resection for primary sporadic colorectal cancer, and from 114 patients who had undergone colonoscopy at the Municipal Hospital in Jaworzno (Poland).Paraffin-embedded, 4-µm-thick tissue sections were stained for rabbit polyclonal anti SOD2 antibody obtained from GeneTex (clone TF9-10-H10 from America Diagnostica).

Results: Results of our study demonstrated that the development of colorectal cancer is connected with increased expression of MnSOD both in adenoma and adenocarcinoma stages. Samples of adenocarcinoma with G2 and G3 grade showed significantly higher levels of immunohistochemical expression of this antioxidant enzyme. Moreover, patients with the presence of lymphovascular invasion and higher degree of regional lymph node status have been also characterised by higher levels of MnSOD expression. The samples of adenoma have been characterised by higher levels of MnSOD expression in comparison to normal mucosa as well. Interestingly, there was no significant correlation between expression and histological type of adenoma.

Conclusions: Development of colorectal cancer is connected with increased expression of MnSOD both in adenoma and adenocarcinoma stages.
keywords:

colorectal cancer, colorectal adenoma, manganese superoxide dismutase, immunohistochemistry, oxidative stress

references:
Kowaltowski AJ, Souza-Pinto NC, Castilho RF, Vercesi AE. Mitochondria and reactive oxygen species. Free Radic Biol Med 2009; 47: 333-43.
Dan DJ, Alvarez LA, Zhang X, Soldati T. Reactive oxygen species and mitochondria: a nexus of cellular homeostasis. Redox Biol 2015; 6: 472-85.
Keyer K, Gort AS, Imlay JA. Superoxide and the production of oxidative DNA damage. J Bacteriol 1995; 177: 6782-90.
Brand MD, Affourtit C, Esteves TC, et al. Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins. Free Radic Biol Med 2004; 37: 755-67.
Pervaiz S, Clement MV. Superoxide anion: oncogenic reactive species? Int J Biochem Cell Biol 2007; 39: 1297-304.
Sies H. Strategies of antioxidant defense. Eur J Biochem 1993; 215: 213-9.
Zelko IN, Mariani TJ, Folz RJ. Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med 2002; 33: 337-49.
Imlay JA. Cellular defense against superoxide and hydrogen peroxide. Annu Rev Biochem 2008; 77: 755-76.
Dhar SK, Clair DK. Manganese superoxide regulation and cancer. Free Radic Biol Med 2012; 52: 2209-22.
Świątkowski M, Medre A, Sobczyński L. Adenomas detected during screening colonoscopies in the years 2000-2009. Prz Gastroenterol 2012; 7: 299-305.
Tsao JL, Tavare S, Salovaara R, et al. Colorectal adenoma and cancer divergence. Evidence and multilineage progression. Am J Pathol 1999; 154: 1815-24.
Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol 2014; 24: 453-62.
Starkov AA. The role of mitochondria in reactive oxygen species metabolism and signaling. Ann N Y Acad Sci 2008; 1147: 37-52.
Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 2012; 24: 981-90.
Connor KM, Hempel N, Nelson KK, et al. Manganese superoxide dismutase enhances the invasive and migratory activity of tumor cells. Cancer Res 2007; 67: 10260-7.
Kattan Z, Mining V, Leroy P, et al. Role of manganese superoxide dismutase on growth and invasive properties of human estrogen-independent breast cancer cells. Breast Cancer Res Treat 2008; 108: 203-15.
Hempel N, Ye H, Abessi B. Altered redox status accompanies progression to metastatic human bladder cancer. Free Radic Biol Med 2009; 46: 42-50.
Liu Z, Li S, Cai Y, et al. Manganese superoxide dismutase indu­ces migration and invasion of tongue squamous cell carcinoma via H202-dependent Snail signaling. Free Radic Biol Med 2012; 53: 44-50.
Izutani R, Asanom S, Imano M, et al. Expression of superoxide dismutase in esophageal and gastric cancers. J Gastroenterol 1998; 33: 816-22.
Hermann B, Li Y, Ray MB, et al. Association of manganese superoxide dismutase expression wit progression of carcinogenesis in Barret esophagus. Arch Surg Oncol 2007; 14: 2045-55.
Li Y, Wo JM, Su RR, et al. Alterations in manganese superoxide dismutase expression in the progression from reflux esophagitis to esophageal adenocarcinoma. Ann Surg Oncol 2007; 14: 2045-55.
Izutani R, Kato M, Assano S, et al. Expression of manganese superoxide dismutase influences chemosensitivity in esophageal and gastric cancer. Cancer Detect Prev 2002; 26: 213-21.
Sun GG, Wang YD, Lu YF, Hu WN. Different association of manganese superoxide dismutase gene polymorphism with risk of prostate, esophageal, and lung cancers: evidence from meta-analysis of 20,025 subjects. Asian Pacific J Cancer Prev 2013; 14: 1937-43.
Janssen AM, Bosman CB, van Duijn W, et al. Superoxide dismutase in gastric and esophageal cancer and the prognostic impact in gastric cancer. Clin Cancer Res 2000; 6: 3183-92.
Ye H, Wang A, Lee BS, et al. Proteomic based identification of manganese superoxide dismutase 2 (SOD2) as a metastasis marker for oral squamous cell carcinoma. Cancer Gen Prot 2008; 5: 85-93.
Lewis A, Du J, Liu J, et al. Metastatic progression of pancreatic cancer: changes in antioxidant enzymes and cell growth. Clin Exp Metastasis 2005; 22: 523-32.
Nozoe T, Honda M, Inatsuka S, et al. Significance of immunohistochemical expression of manganese superoxide dismutase as a marker of malignant potential in colorectal carcinoma. Oncol Rep 2003; 10: 39-43.
Malafa M, Margenthaler j, Webb B, et al. MnSOD expression is increased in metastatic gastric cancer. J Surg Res 2000; 88: 130-4.
Ni J, Mei M, Sun L. Oxidative DNA damage and repair in chronic atrophic gastritis and gastric cancer. Hepatogastroenterology 2012; 59: 671-5.
Hwang TS, Choi HK, Han HS. Differential expression of manganese superoxide dismutase, copper/zinc superoxide dismutase, and catalase in gastric adenocarcinoma and normal gastric mucosa. Eur J Surg Oncol 2007; 33: 474-9.
Monari M, Foschi J, Calabrese C, et al. Implications of antioxidant enzymes in human gastric neoplasms. Int J Mol Med 2009; 24: 693-700.
Izutani R, Katoh M, Asano S, et al. Enhanced expression of manganese superoxide dismutase mRNA and increased TNF­alpha mRNA expression by gastric mucosa in gastric cancer. World J Surg 1996; 20: 228-33.
Hempel N, Carrico PM, Melendez JA. Manganese superoxide dismutase (SOD2) and redox-control of signaling events that drive metastasis. Anticancer Agents Med Chem 2011; 11: 191-201.
Tsuji T, Ibargi S, Hu GF. Epithelial-mesenchymal transition and cell cooperativity in metastasis. Cancer Res 2009; 69: 7135-9.
Nathan CF. Neutrophil activation on biological surfaces. Massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes. J Clin Invest 1987; 80: 1550-60.
Kruidenier L, Kuiper I, van Duijn W, et al. Differential mucosal expression of three superoxide dismutase isoforms in inflammatory bowel disease. J Pathol 2003; 201: 7-16.
Hil MJ, Morson BC, Bussey HJ. Aetiology of adenoma-carcinoma sequence in large bowel Lancet 1978; 1: 245-7.
Shinya H, Wolff WI. Morphology, anatomic distribution and cancer potential of colonic polyps. Ann Surg 1979; 190: 679-83.
Gilles RJ, Robey I, Gatenby RA. Causes and consequence of increased glucose metabolism of cancers. J Nucl Med 2008; 49: 24S-42S.
Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009; 324: 1029-33.
Newsholme EA, Crabtree B, Ardawi MS. The role of high rates of glycolysis and glutamine utilization in rapidly dividing cells. Biosci Rep 1985; 5: 393-400.
Gatenby RA, Gilles RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer 2004; 4: 891-9.
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