Alteration of extracellular superoxide dismutase expression is associated with an aggressive phenotype of oral squamous-cell carcinoma

Yokoe,Hidetaka; Nomura,Hitomi; Yamano,Yukio; Fushimi,Kazuaki; Sakamoto,Yosuke; Ogawara,Katsunori; Shiiba,Masashi; Bukawa,Hiroki; Uzawa,Katsuhiro; Takiguchi,Yuichi; Tanzawa,Hideki

doi:10.3892/etm_00000092

Alteration of extracellular superoxide dismutase expression is associated with an aggressive phenotype of oral squamous-cell carcinoma

Authors:
- Hidetaka Yokoe
- Hitomi Nomura
- Yukio Yamano
- Kazuaki Fushimi
- Yosuke Sakamoto
- Katsunori Ogawara
- Masashi Shiiba
- Hiroki Bukawa
- Katsuhiro Uzawa
- Yuichi Takiguchi
- Hideki Tanzawa
View Affiliations

Affiliations: Division of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8670, Japan
Published online on: July 1, 2010 https://doi.org/10.3892/etm_00000092
Pages: 585-590

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Oxidative stress results in damage to cellular structures and has been linked to numerous diseases, including cancer. Extracellular superoxide dismutase (EC-SOD) is a principal enzymatic antioxidant in extracellular space. The purpose of this study was to determine whether the expression of EC-SOD protein is altered in the carcinogenetic process of oral squamous-cell carcinoma (OSCC). Immunohistochemical analysis was carried out in matched normal and tumour specimens collected from 58 OSCCs and 20 oral premalignant lesions (OPLs). Correlations between the EC-SOD expression levels and clinicopathological features of OSCC patients were evaluated by Fisher's exact test. Although EC-SOD protein was consistently expressed on the plasma membrane of cells in normal tissues, plasma membranous EC-SOD expression was lost in almost all the OSCC specimens examined (98%). Instead, positive EC-SOD expression was detected in the cytoplasmic compartments of cancerous cells in both OPLs (65%) and OSCCs (52%), together with a high incidence of lymph node metastasis (p=0.0397). These results suggest that the dysregulation of EC-SOD protein expression is a frequently occuring and early event in oral carcinogenesis, and that cytoplasmic EC-SOD may contribute to the increased aggressiveness of OSCC.

View Figures

View References

1.	Ferlay J, Bray P, Pisani P and Parkin DM: GLOBOCAN 2002: Cancer Incidence, Mortalityand Prevalence Worldwide. IARC Cancer Base No. 5, version 2.0. IARC Press; Lyon: 2004
2.	La Vecchia C, Lucchini F, Negri E and Levi F: Trends in oral cancer mortality in Europe. Oral Oncol. 40:433–439. 2004.
3.	Valko M, Rhodes CJ, Moncol J, Izakovic M and Mazur M: Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 160:1–40. 2006. View Article : Google Scholar : PubMed/NCBI
4.	Klaunig JE and Kamendulis LM: The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol. 44:239–267. 2004. View Article : Google Scholar : PubMed/NCBI
5.	Oberley LW, Oberley TD and Buettner GR: Cell division in normal and transformed cells: the possible role of superoxide and hydrogen peroxide. Med Hypoth. 7:21–42. 1981. View Article : Google Scholar : PubMed/NCBI
6.	Spitz DS, Sim JE, Ridnour LA, Galoforo SS and Lee YJ: Glucose deprivation-induced oxidative stress in human tumor cells: a fundamental defect in metabolism? Ann NY Acad Sci. 899:349–362. 2000. View Article : Google Scholar : PubMed/NCBI
7.	Valko M, Izakovic M, Mazur M, Rhodes CJ and Telser J: Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem. 266:37–56. 2004. View Article : Google Scholar : PubMed/NCBI
8.	Franco R, Schoneveld O, Georgakilas AG and Panayiotidis MI: Oxidative stress, DNA methylation and carcinogenesis. Cancer Lett. 266:6–11. 2008. View Article : Google Scholar : PubMed/NCBI
9.	Gromadzińska J and Wasowicz W: The role of reactive oxygen species in the development of malignancies. Int J Occup Med Environ Health. 13:233–245. 2000.
10.	Kuznetsov AV, Smigelskaite J, Doblander C, et al: Survival signaling by C-RAF: mitochondrial reactive oxygen species and Ca2+ are critical targets. Mol Cell Biol. 28:2304–2313. 2008.PubMed/NCBI
11.	Cho HJ, Jeong HG, Lee JS, et al: Oncogenic H-Ras enhances DNA repair through the Ras/phosphatidylinositol 3-kinase/Rac1 pathway in NIH3T3 cells. Evidence for association with reactive oxygen species. J Biol Chem. 277:19358–19366. 2002. View Article : Google Scholar : PubMed/NCBI
12.	Blokhina O, Virolainen E and Fagerstedt KV: Antioxidants, oxidative damage and oxygen deprivation stress: a review. Ann Bot. 91:179–194. 2003. View Article : Google Scholar : PubMed/NCBI
13.	Liochev SI and Fridovich I: The effects of superoxide dismutase on H2O2 formation. Free Radic Biol Med. 42:1465–1469. 2007. View Article : Google Scholar : PubMed/NCBI
14.	Hileman EA, Achanta G and Huang P: Superoxide dismutase: an emerging target for cancer therapeutics. Expert Opin Ther Targets. 5:697–710. 2001. View Article : Google Scholar : PubMed/NCBI
15.	Kinnula VL and Crapo JD: Superoxide dismutases in malignant cells and human tumors. Free Radic Biol Med. 36:718–744. 2004. View Article : Google Scholar : PubMed/NCBI
16.	Zelko IN, Mariani TJ and 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. 33:337–349. 2002. View Article : Google Scholar : PubMed/NCBI
17.	Sandström J, Karlsson K, Edlund T and Marklund SL: Heparin-affinity patterns and composition of extracellular superoxide dismutase in human plasma and tissues. Biochem J. 294:853–857. 1993.PubMed/NCBI
18.	Moriarty-Craige SE and Jones DP: Extracellular thiols and thiol/disulfide redox in metabolism. Annu Rev Nutr. 24:481–509. 2004. View Article : Google Scholar : PubMed/NCBI
19.	Nakamura H, Masutani H and Yodoi J: Extracellular thioredoxin and thioredoxin-binding protein 2 in control of cancer. Semin Cancer Biol. 16:444–451. 2006. View Article : Google Scholar : PubMed/NCBI
20.	Rees MD, Kennett EC, Whitelock JM and Davies MJ: Oxidative damage to extracellular matrix and its role in human pathologies. Free Radic Biol Med. 44:1973–2001. 2008. View Article : Google Scholar : PubMed/NCBI
21.	Bilalovic N, Sandstad B, Golouh R, et al: CD10 protein expression in tumor and stromal cells of malignant melanoma is associated with tumor progression. Mod Pathol. 17:1251–1258. 2004. View Article : Google Scholar : PubMed/NCBI
22.	McCarty KS Jr, Szabo E, Flowers JL, et al: Use of monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors. Cancer Res. 46:4244–4248. 1986.PubMed/NCBI
23.	Amagasa T, Yamashiro M and Ishikawa H: Oral leukoplakia related to malignant transformation. Oral Sci Int. 3:45–55. 2006. View Article : Google Scholar
24.	Kim SH, Kim MO, Gao P, et al: Overexpression of extracellular superoxide dismutase (EC-SOD) in mouse skin plays a protective role in DMBA/TPA-induced tumor formation. Oncol Res. 15:333–341. 2005.PubMed/NCBI
25.	Wheeler MD, Smutney OM and Samulski RJ: Secretion of extracellular superoxide dismutase from muscle transduced with recombinant adenovirus inhibits the growth of B16 melanomas in mice. Mol Cancer Res. 1:871–881. 2003.PubMed/NCBI
26.	Chaiswing L, Zhong W, Cullen JJ, Oberley LW and Oberley TD: Extracellular redox state regulates features associated with prostate cancer cell invasion. Cancer Res. 68:5820–5826. 2008. View Article : Google Scholar : PubMed/NCBI
27.	Sandström J, Nilsson P, Karlsson K and Marklund SL: 10-fold increase in human plasma extracellular superoxide dismutase content caused by a mutation in heparin-binding domain. J Biol Chem. 269:19163–19166. 1994.PubMed/NCBI
28.	Horton P, Park KJ, Obayashi T, et al: WoLF PSORT: protein localization predictor. Nucleic Acids Res. 35:585–587. 2007. View Article : Google Scholar
29.	Connor KM, Hempel N, Nelson KK, et al: Manganese super-oxide dismutase enhances the invasive and migratory activity of tumor cells. Cancer Res. 67:10260–10267. 2007. View Article : Google Scholar : PubMed/NCBI
30.	Kim JJ, Chae SW, Hur GC, et al: Manganese superoxide dismutase expression correlates with a poor prognosis in gastric cancer. Pathobiology. 70:353–360. 2003. View Article : Google Scholar : PubMed/NCBI
31.	Janssen AM, Bosman CB, Sier CF, et al: Superoxide dismutases in relation to the overall survival of colorectal cancer patients. Br J Cancer. 78:1051–1057. 1998. View Article : Google Scholar : PubMed/NCBI
32.	Yokoe H, Nomura H, Yamano Y, et al: Characterization of intra-cellular superoxide dismutase alterations in premalignant and malignant lesions of the oral cavity: correlation with lymph node metastasis. J Cancer Res Clin Oncol. 135:1625–1633. 2009. View Article : Google Scholar : PubMed/NCBI