Skip to main content
Top
Published in: Virchows Archiv 6/2017

01-12-2017 | Original Article

Nrf2-peroxiredoxin I axis in polymorphous adenocarcinoma is associated with low matrix metalloproteinase 2 level

Authors: J. M. Brod, Ana Paula Dias Demasi, V. A. Montalli, L. N. Teixeira, C. Furuse, M. C. Aguiar, A. B. Soares, M. Sperandio, V. C. Araujo

Published in: Virchows Archiv | Issue 6/2017

Login to get access

Abstract

Polymorphous adenocarcinoma (PAC) is a malignant epithelial neoplasm that affects almost exclusively the minor salivary glands, generally described as having a relatively good prognosis. Aberrant nuclear factor erythroid 2 (NF-E2)-related factor (Nrf2) activation in tumor cells has been associated with induction of antioxidant enzymes, such as peroxiredoxin I (Prx I) and increased matrix metalloproteinase (MMP) expression. In this context, the aim of the present study was to evaluate the expression of Nrf2 and correlate it with Prx I and MMP-2 secretion in PAC. Thirty-one cases of PAC from oral biopsies were selected and immunohistochemically analyzed for Nrf2 and Prx I. MMP-2 quantification was performed on primary cell cultures derived from PAC. Oral squamous cell carcinoma (OSCC) cell cultures were used as control. A high immunoexpression of Nrf2 was observed in both the cytoplasm and the nucleus of neoplastic cells from PAC. Nuclear staining for Nrf2 suggested its activation in the majority of the PAC cells, which was confirmed by the high expression of its target gene, Prx I. Quantification of MMP-2 secretion showed lower levels in PAC cell cultures when compared to OSCC cell cultures (p < 0.05). In conclusion, although Nrf2 overexpression has been frequently associated with high-grade malignancies, such relationship is not infallible and, in fact, the opposite may occur in low-grade tumors, such as PAC of minor salivary glands.
Literature
1.
go back to reference Fonseca I, Assaad A, Katabi N et al (2017) Polymorphous adenocarcinoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumors, 4th edn. IARC, Lyon, pp 167–168 Fonseca I, Assaad A, Katabi N et al (2017) Polymorphous adenocarcinoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds) WHO classification of head and neck tumors, 4th edn. IARC, Lyon, pp 167–168
2.
go back to reference Patel TD, Vazquez A, Marchiano E et al (2015) Polymorphous low-grade adenocarcinoma of the head and neck: a population-based study of 460 cases. Laryngoscope 125:1644–1649CrossRefPubMed Patel TD, Vazquez A, Marchiano E et al (2015) Polymorphous low-grade adenocarcinoma of the head and neck: a population-based study of 460 cases. Laryngoscope 125:1644–1649CrossRefPubMed
3.
go back to reference Paleri V, Robinson M, Bradley P (2008) Polymorphous low-grade adenocarcinoma of the head and neck. Curr Opin Otolaryngol Head Neck Surg 16:163–169CrossRefPubMed Paleri V, Robinson M, Bradley P (2008) Polymorphous low-grade adenocarcinoma of the head and neck. Curr Opin Otolaryngol Head Neck Surg 16:163–169CrossRefPubMed
4.
go back to reference Araújo V, Sousa S, Jaeger M et al (1999) Characterization of the cellular component of polymorphous low-grade adenocarcinoma by immunohistochemistry and electron microscopy. Oral Oncol 35:164–172CrossRefPubMed Araújo V, Sousa S, Jaeger M et al (1999) Characterization of the cellular component of polymorphous low-grade adenocarcinoma by immunohistochemistry and electron microscopy. Oral Oncol 35:164–172CrossRefPubMed
5.
go back to reference Klaunig JE, Wang Z, Pu X et al (2011) Oxidative stress and oxidative damage in chemical carcinogenesis. Toxicol Appl Pharmacol 254:86–99CrossRefPubMed Klaunig JE, Wang Z, Pu X et al (2011) Oxidative stress and oxidative damage in chemical carcinogenesis. Toxicol Appl Pharmacol 254:86–99CrossRefPubMed
6.
go back to reference Moi P, Chan K, Asunis I et al (1994) Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci U S A 91:9926–9930CrossRefPubMedPubMedCentral Moi P, Chan K, Asunis I et al (1994) Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci U S A 91:9926–9930CrossRefPubMedPubMedCentral
7.
go back to reference Itoh K, Chiba T, Takahashi S et al (1997) An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 236:313–322CrossRefPubMed Itoh K, Chiba T, Takahashi S et al (1997) An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 236:313–322CrossRefPubMed
8.
go back to reference Giudice A, Arra C, Turco MC (2010) Review of molecular mechanisms involved in the activation of the Nrf2-ARE signaling pathway by chemopreventive agents. Methods Mol Biol 647:37–74CrossRefPubMed Giudice A, Arra C, Turco MC (2010) Review of molecular mechanisms involved in the activation of the Nrf2-ARE signaling pathway by chemopreventive agents. Methods Mol Biol 647:37–74CrossRefPubMed
9.
go back to reference Kim YJ, Ahn JY, Liang P et al (2007) Human prx1 gene is a target of Nrf2 and is up-regulated by hypoxia/reoxygenation: implication to tumor biology. Cancer Res 67:546–554CrossRefPubMed Kim YJ, Ahn JY, Liang P et al (2007) Human prx1 gene is a target of Nrf2 and is up-regulated by hypoxia/reoxygenation: implication to tumor biology. Cancer Res 67:546–554CrossRefPubMed
10.
go back to reference Kang SW, Rhee SG, Chang TS et al (2005) 2-Cys peroxiredoxin function in intracellular signal transduction: therapeutic implications. Trends Mol Med 11:571–578CrossRefPubMed Kang SW, Rhee SG, Chang TS et al (2005) 2-Cys peroxiredoxin function in intracellular signal transduction: therapeutic implications. Trends Mol Med 11:571–578CrossRefPubMed
12.
go back to reference Ding C, Fan X, Wu G (2017) Peroxiredoxin 1—an antioxidant enzyme in cancer. J Cell Mol Med 21:193–202CrossRefPubMed Ding C, Fan X, Wu G (2017) Peroxiredoxin 1—an antioxidant enzyme in cancer. J Cell Mol Med 21:193–202CrossRefPubMed
13.
go back to reference Slocum SL, Kensler TW (2011) Nrf2: control of sensitivity to carcinogens. Arch Toxicol 85:273–284CrossRefPubMed Slocum SL, Kensler TW (2011) Nrf2: control of sensitivity to carcinogens. Arch Toxicol 85:273–284CrossRefPubMed
14.
15.
go back to reference Aoki Y, Sato H, Nishimura N et al (2001) Accelerated DNA adduct formation in the lung of the Nrf2 knockout mouse exposed to diesel exhaust. Toxicol Appl Pharmacol 173:154–160CrossRefPubMed Aoki Y, Sato H, Nishimura N et al (2001) Accelerated DNA adduct formation in the lung of the Nrf2 knockout mouse exposed to diesel exhaust. Toxicol Appl Pharmacol 173:154–160CrossRefPubMed
16.
go back to reference Na HK, Surh YJ (2014) Oncogenic potential of Nrf2 and its principal target protein heme oxygenase-1. Free Radic Biol Med 67:353–365CrossRefPubMed Na HK, Surh YJ (2014) Oncogenic potential of Nrf2 and its principal target protein heme oxygenase-1. Free Radic Biol Med 67:353–365CrossRefPubMed
17.
go back to reference Sporn MB, Liby KT (2012) NRF2 and cancer: the good, the bad and the importance of context. Nat Rev Cancer 12:564–571CrossRefPubMed Sporn MB, Liby KT (2012) NRF2 and cancer: the good, the bad and the importance of context. Nat Rev Cancer 12:564–571CrossRefPubMed
18.
go back to reference Chartoumpekis DV, Wakabayashi N, Kensler TW (2015) Keap1/Nrf2 pathway in the frontiers of cancer and non-cancer cell metabolism. Biochem Soc Trans 43:639–644CrossRefPubMedPubMedCentral Chartoumpekis DV, Wakabayashi N, Kensler TW (2015) Keap1/Nrf2 pathway in the frontiers of cancer and non-cancer cell metabolism. Biochem Soc Trans 43:639–644CrossRefPubMedPubMedCentral
19.
go back to reference Xiang M, Namani A, Wu S et al (2014) Nrf2: bane or blessing in cancer? J Cancer Res Clin Oncol 140:1251–1259CrossRefPubMed Xiang M, Namani A, Wu S et al (2014) Nrf2: bane or blessing in cancer? J Cancer Res Clin Oncol 140:1251–1259CrossRefPubMed
20.
go back to reference Gañán-Gómez I, Wei Y, Yang H et al (2013) Oncogenic functions of the transcription factor Nrf2. Free Radic Biol Med 65:750–764CrossRefPubMed Gañán-Gómez I, Wei Y, Yang H et al (2013) Oncogenic functions of the transcription factor Nrf2. Free Radic Biol Med 65:750–764CrossRefPubMed
21.
go back to reference Pan H, Wang H, Zhu L et al (2013) The role of Nrf2 in migration and invasion of human glioma cell U251. World Neurosurg 80:363–370CrossRefPubMed Pan H, Wang H, Zhu L et al (2013) The role of Nrf2 in migration and invasion of human glioma cell U251. World Neurosurg 80:363–370CrossRefPubMed
22.
go back to reference Zhang M, Zhang C, Zhang L et al (2015) Nrf2 is a potential prognostic marker and promotes proliferation and invasion in human hepatocellular carcinoma. BMC Cancer 15:531CrossRefPubMedPubMedCentral Zhang M, Zhang C, Zhang L et al (2015) Nrf2 is a potential prognostic marker and promotes proliferation and invasion in human hepatocellular carcinoma. BMC Cancer 15:531CrossRefPubMedPubMedCentral
23.
go back to reference Tertil M, Golda S, Skrzypek K et al (2015) Nrf2-heme oxygenase-1 axis in mucoepidermoid carcinoma of the lung: antitumoral effects associated with down-regulation of matrix metalloproteinases. Free Radic Biol Med 89:147–157CrossRefPubMed Tertil M, Golda S, Skrzypek K et al (2015) Nrf2-heme oxygenase-1 axis in mucoepidermoid carcinoma of the lung: antitumoral effects associated with down-regulation of matrix metalloproteinases. Free Radic Biol Med 89:147–157CrossRefPubMed
25.
go back to reference Yanagawa T, Iwasa S, Ishii T et al (2000) Peroxiredoxin I expression in oral cancer: a potential new tumor marker. Cancer Lett 156:27–35CrossRefPubMed Yanagawa T, Iwasa S, Ishii T et al (2000) Peroxiredoxin I expression in oral cancer: a potential new tumor marker. Cancer Lett 156:27–35CrossRefPubMed
26.
27.
go back to reference Lee EY, Kang JY, Kim KW (2015) Expression of cyclooxygenase-2, peroxiredoxin I, peroxiredoxin 6 and nuclear factor-κB in oral squamous cell carcinoma. Oncol Lett 10:3129–3136PubMedPubMedCentral Lee EY, Kang JY, Kim KW (2015) Expression of cyclooxygenase-2, peroxiredoxin I, peroxiredoxin 6 and nuclear factor-κB in oral squamous cell carcinoma. Oncol Lett 10:3129–3136PubMedPubMedCentral
28.
go back to reference Gao ZB, Duan YQ, Zhang L, Chen DW, Ding PT et al (2005) Expression of matrix metalloproteinase 2 and its tissue inhibitor in oral squamous cell carcinoma. Int J Mol Med 16:599–603PubMed Gao ZB, Duan YQ, Zhang L, Chen DW, Ding PT et al (2005) Expression of matrix metalloproteinase 2 and its tissue inhibitor in oral squamous cell carcinoma. Int J Mol Med 16:599–603PubMed
29.
go back to reference Lawal AO, Adisa AO, Kolude B et al (2015) Immunohistochemical expression of MMP-2 and MMP-8 in oral squamous cell carcinoma. J Clin Exp Dent 1:e203–e207CrossRef Lawal AO, Adisa AO, Kolude B et al (2015) Immunohistochemical expression of MMP-2 and MMP-8 in oral squamous cell carcinoma. J Clin Exp Dent 1:e203–e207CrossRef
30.
go back to reference Gontarz M, Wyszyńska-Pawelec G, Zapała J et al (2016) Immunohistochemical predictors in squamous cell carcinoma of the tongue and floor of the mouth. Head Neck 38(Suppl 1):E747–E753CrossRefPubMed Gontarz M, Wyszyńska-Pawelec G, Zapała J et al (2016) Immunohistochemical predictors in squamous cell carcinoma of the tongue and floor of the mouth. Head Neck 38(Suppl 1):E747–E753CrossRefPubMed
31.
go back to reference Shrestha B, Bajracharya D, Byatnal AA et al (2017) May high mmp-2 and timp-2 expressions increase or decrease the aggressivity of oral cancer? Pathol Oncol Res 23:197–206CrossRefPubMed Shrestha B, Bajracharya D, Byatnal AA et al (2017) May high mmp-2 and timp-2 expressions increase or decrease the aggressivity of oral cancer? Pathol Oncol Res 23:197–206CrossRefPubMed
32.
go back to reference Teixeira LN, Montalli VAM, de Oliveira SBP et al (2017) Establishment of a primary culture of polymorphous low grade adenocarcinoma cells. Arch Oral Biol 15:188–193CrossRef Teixeira LN, Montalli VAM, de Oliveira SBP et al (2017) Establishment of a primary culture of polymorphous low grade adenocarcinoma cells. Arch Oral Biol 15:188–193CrossRef
33.
go back to reference Droździk A, Kowalczyk R, Jaworowska E et al (2015) The role of Nrf2 in pathology of pleomorphic adenoma in parotid gland. Med Sci Monit 30:1243–1248 Droździk A, Kowalczyk R, Jaworowska E et al (2015) The role of Nrf2 in pathology of pleomorphic adenoma in parotid gland. Med Sci Monit 30:1243–1248
34.
go back to reference Huang CF, Deng WW, Zhang L et al (2016) Expression of LC3, LAMP2, KEAP1 and NRF2 in salivary adenoid cystic carcinoma. Pathol Oncol Res 22:109–114CrossRefPubMed Huang CF, Deng WW, Zhang L et al (2016) Expression of LC3, LAMP2, KEAP1 and NRF2 in salivary adenoid cystic carcinoma. Pathol Oncol Res 22:109–114CrossRefPubMed
35.
go back to reference Li C, Jackson RM (2002) Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol 282:C227–C241CrossRefPubMed Li C, Jackson RM (2002) Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol 282:C227–C241CrossRefPubMed
36.
37.
go back to reference Wang J, Zhang M, Zhang L et al (2010) Correlation of Nrf2,HO-1, and MRP3 in gallbladder cancer and their relationships to clinicopathologic features and survival. J Surg Res 164:e99–105CrossRefPubMed Wang J, Zhang M, Zhang L et al (2010) Correlation of Nrf2,HO-1, and MRP3 in gallbladder cancer and their relationships to clinicopathologic features and survival. J Surg Res 164:e99–105CrossRefPubMed
38.
go back to reference Tsai JR, Wang HM, Liu PL et al (2012) High expression of heme oxygenase-1 is associated with tumor invasiveness and poor clinical outcome in non-small cell lung cancer patients. Cell Oncol (Dordr) 35:461–471CrossRef Tsai JR, Wang HM, Liu PL et al (2012) High expression of heme oxygenase-1 is associated with tumor invasiveness and poor clinical outcome in non-small cell lung cancer patients. Cell Oncol (Dordr) 35:461–471CrossRef
39.
go back to reference Yin Y, Liu Q, Wang B et al (2012) Expression and function of heme oxygenase-1 in human gastric cancer. Exp Biol Med (Maywood) 237:362–371CrossRef Yin Y, Liu Q, Wang B et al (2012) Expression and function of heme oxygenase-1 in human gastric cancer. Exp Biol Med (Maywood) 237:362–371CrossRef
40.
go back to reference Fan J, Wu FY, Wang L et al (2011) Comparative expression of matrix metalloproteinases in low-grade mucoepidermoid carcinoma and typical lung cancer. Oncol Lett 2:1269–1273PubMedPubMedCentral Fan J, Wu FY, Wang L et al (2011) Comparative expression of matrix metalloproteinases in low-grade mucoepidermoid carcinoma and typical lung cancer. Oncol Lett 2:1269–1273PubMedPubMedCentral
Metadata
Title
Nrf2-peroxiredoxin I axis in polymorphous adenocarcinoma is associated with low matrix metalloproteinase 2 level
Authors
J. M. Brod
Ana Paula Dias Demasi
V. A. Montalli
L. N. Teixeira
C. Furuse
M. C. Aguiar
A. B. Soares
M. Sperandio
V. C. Araujo
Publication date
01-12-2017
Publisher
Springer Berlin Heidelberg
Published in
Virchows Archiv / Issue 6/2017
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-017-2218-8

Other articles of this Issue 6/2017

Virchows Archiv 6/2017 Go to the issue