DOI QR코드

DOI QR Code

Hydrogen Peroxide Promotes Epithelial to Mesenchymal Transition and Stemness in Human Malignant Mesothelioma Cells

  • Kim, Myung-Chul (Laboratory of Clinical Pathology, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University) ;
  • Cui, Feng-Ji (Laboratory of Clinical Pathology, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University) ;
  • Kim, Yongbaek (Laboratory of Clinical Pathology, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University)
  • Published : 2013.06.30

Abstract

Reactive oxygen species (ROS) are known to promote mesothelial carcinogenesis that is closely associated with asbestos fibers and inflammation. Epithelial to mesenchymal cell transition (EMT) is an important process involved in the progression of tumors, providing cancer cells with aggressiveness. The present study was performed to determine if EMT is induced by $H_2O_2$ in human malignant mesothelioma (HMM) cells. Cultured HMM cells were treated with $H_2O_2$, followed by measuring expression levels of EMT-related genes and proteins. Immunohistochemically, TWIST1 expression was confined to sarcomatous cells in HMM tissues, but not in epithelioid cells. Treatment of HMM cells with $H_2O_2$ promoted EMT, as indicated by increased expression levels of vimentin, SLUG and TWIST1, and decreased E-cadherin expression. Expression of stemness genes such as OCT4, SOX2 and NANOG was also significantly increased by treatment of HMM cells with $H_2O_2$. Alteration of these genes was mediated via activation of hypoxia inducible factor 1 alpha (HIF-$1{\alpha}$) and transforming growth factor beta 1 (TGF-${\beta}1$). Considering that treatment with $H_2O_2$ results in excess ROS, the present study suggests that oxidative stress may play a critical role in HMM carcinogenesis by promoting EMT processes and enhancing the expression of stemness genes.

Keywords

Mesothelioma;reactive oxygen species;epithelial to mesenchymal transition;stemness;$HIF1{\alpha}$

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

References

  1. Abutaily AS, Collins JE, Roche WR (2003). Cadherins, catenins and APC in pleural malignant mesothelioma. J Pathol, 201, 355-62. https://doi.org/10.1002/path.1458
  2. Cannito S, Novo E, Compagnone A, et al (2008). Redox mechanisms switch on hypoxia-dependent epithelialmesenchymal transition in cancer cells. Carcinogenesis, 29, 2267-78. https://doi.org/10.1093/carcin/bgn216
  3. Carbone M, Kratzke RA, Testa JR (2002). The pathogenesis of mesothelioma. Semin Oncol, 29, 2-17. https://doi.org/10.1016/S0093-7754(02)70081-X
  4. Clerkin JS, Naughton R, Quiney C, Cotter TG (2008). Mechanisms of ROS modulated cell survival during carcinogenesis. Cancer Lett, 266, 30-6. https://doi.org/10.1016/j.canlet.2008.02.029
  5. Edelman GM, Gallin WJ, Delouvee A, Cunningham BA, Thiery JP (1983). Early epochal maps of two different cell adhesion molecules. Proc Natl Acad Sci USA, 80, 4384-8. https://doi.org/10.1073/pnas.80.14.4384
  6. Geiger TR, Peeper DS (2009). Metastasis mechanisms. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1796, 293-308. https://doi.org/10.1016/j.bbcan.2009.07.006
  7. Gustafsson MV, Zheng X, Pereira T, et al (2005). Hypoxia requires notch signaling to maintain the undifferentiated cell state. Developmental cell, 9, 617-28. https://doi.org/10.1016/j.devcel.2005.09.010
  8. Hong HH, Dunnick J, Herbert R, et al (2007). Genetic alterations in K-ras and p53 cancer genes in lung neoplasms from Swiss (CD-1) male mice exposed transplacentally to AZT. Environ Mol Mutagen, 48, 299-306. https://doi.org/10.1002/em.20197
  9. Huang SX, Partridge MA, Ghandhi SA, et al (2012). Mitochondria-derived reactive intermediate species mediate asbestos-induced genotoxicity and oxidative stress-responsive signaling pathways. Environmental Hlth Perspectives, 120, 840-7. https://doi.org/10.1289/ehp.1104287
  10. Kai K, D’Costa S, Yoon BI, et al (2010). Characterization of side population cells in human malignant mesothelioma cell lines. Lung Cancer, 70, 146-51. https://doi.org/10.1016/j.lungcan.2010.04.020
  11. Kang Y, Massague J (2004). Epithelial-mesenchymal transitions: twist in development and metastasis. Cell, 118, 277-9. https://doi.org/10.1016/j.cell.2004.07.011
  12. Kim HM, Haraguchi N, Ishii H, Ohkuma M, Okano M, Mimori K, et al. (2012). Increased CD13 expression reduces reactive oxygen species, promoting survival of liver cancer stem cells via an epithelial-mesenchymal transition-like phenomenon. Annals of Surg Oncology, 19, 539-48. https://doi.org/10.1245/s10434-011-2040-5
  13. Kim Y, Ton TV, DeAngelo AB, Morgan K, Devereux TR, Anna C, et al. (2006). Major carcinogenic pathways identified by gene expression analysis of peritoneal mesotheliomas following chemical treatment in F344 rats. Toxicol Appl Pharmacol, 214, 144-51. https://doi.org/10.1016/j.taap.2005.12.009
  14. Klabatsa A, Sheaff MT, Steele JP, Evans MT, Rudd RM, Fennell DA (2006). Expression and prognostic significance of hypoxia-inducible factor 1alpha (HIF-1alpha) in malignant pleural mesothelioma (MPM). Lung Cancer, 51, 53-9. https://doi.org/10.1016/j.lungcan.2005.07.010
  15. Kobayashi CI, Suda T (2012). Regulation of reactive oxygen species in stem cells and cancer stem cells. J Cell Physiol, 227, 421-30. https://doi.org/10.1002/jcp.22764
  16. Lee HB, Ha H (2007). Mechanisms of epithelial-mesenchymal transition of peritoneal mesothelial cells during peritoneal dialysis. J Korean Med Sci, 22, 943-5. https://doi.org/10.3346/jkms.2007.22.6.943
  17. Liu B, Chen Y, St Clair DK (2008). ROS and p53: a versatile partnership. Free Rad Biol & Med, 44, 1529-35. https://doi.org/10.1016/j.freeradbiomed.2008.01.011
  18. Maynard S, Schurman SH, Harboe C, de Souza-Pinto NC, Bohr VA (2009). Base excision repair of oxidative DNA damage and association with cancer and aging. Carcinogenesis, 30, 2-10.
  19. McCord AM, Jamal M, Shankavaram UT, Lang FF, Camphausen K, Tofilon PJ (2009). Physiologic oxygen concentration enhances the stem-like properties of CD133+ human glioblastoma cells in vitro. Mol Cancer Res, 7, 489-97. https://doi.org/10.1158/1541-7786.MCR-08-0360
  20. Peinado H, Olmeda D, Cano A (2007). Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer, 7, 415-28. https://doi.org/10.1038/nrc2131
  21. Ramos-Nino ME, Scapoli L, Martinelli ML, Mossman BT (2003). Microarray analysis and RNA silencing link fra-1 to cd44 and c-met expression in mesothelioma. Cancer Res, 63, 3539-45.
  22. Ramos-Nino ME, Testa JR, Altomare DA, et al (2006). Cellular and molecular parameters of mesothelioma. J Cell Biochem, 98, 723-34. https://doi.org/10.1002/jcb.20828
  23. Robson EJ, Khaled WT, Abell K, Watson CJ (2006). Epithelialto-mesenchymal transition confers resistance to apoptosis in three murine mammary epithelial cell lines. Differentiation, 74, 254-64. https://doi.org/10.1111/j.1432-0436.2006.00075.x
  24. Kai K, D’Costa S, Sills RC, Kim Y (2009). Inhibition of the insulin-like growth factor 1 receptor pathway enhances the antitumor effect of cisplatin in human malignant mesothelioma cell lines. Cancer Lett, 278, 49-55. https://doi.org/10.1016/j.canlet.2008.12.023
  25. Shimojo Y, Akimoto M, Hisanaga T, et al (2013). Attenuation of reactive oxygen species by antioxidants suppresses hypoxiainduced epithelial-mesenchymal transition and metastasis of pancreatic cancer cells. Clinical & Exp Metastasis, 30, 143-54. https://doi.org/10.1007/s10585-012-9519-8
  26. Singh A, Settleman J (2010). EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene, 29, 4741-51. https://doi.org/10.1038/onc.2010.215
  27. Sivertsen S, Hadar R, Elloul S, et al (2006). Expression of Snail, Slug and Sip1 in malignant mesothelioma effusions is associated with matrix metalloproteinase, but not with cadherin expression. Lung Cancer, 54, 309-17. https://doi.org/10.1016/j.lungcan.2006.08.010
  28. Terauchi M, Kajiyama H, Yamashita M, et al (2007). Possible involvement of TWIST in enhanced peritoneal metastasis of epithelial ovarian carcinoma. Clin Exp Metastasis, 24, 329-39. https://doi.org/10.1007/s10585-007-9070-1
  29. Tse JC, Kalluri R (2007). Mechanisms of metastasis: epithelialto-mesenchymal transition and contribution of tumor microenvironment. J Cell Biochem, 101, 816-29. https://doi.org/10.1002/jcb.21215
  30. Vega S, Morales AV, Ocana OH, et al (2004). Snail blocks the cell cycle and confers resistance to cell death. Genes Dev, 18, 1131-43. https://doi.org/10.1101/gad.294104
  31. Xu J, Lamouille S, Derynck R (2009). TGF-beta-induced epithelial to mesenchymal transition. Cell Res, 19, 156-72. https://doi.org/10.1038/cr.2009.5
  32. Yang MH, Wu KJ (2008a). TWIST activation by hypoxia inducible factor-1 (HIF-1): implications in metastasis and development. Cell Cycle, 7, 2090-6. https://doi.org/10.4161/cc.7.14.6324
  33. Yang MH, Wu MZ, Chiou SH, et al (2008b). Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol, 10, 295-305. https://doi.org/10.1038/ncb1691
  34. Yang Y, Pan X, Lei W, Wang J, Song J (2006). Transforming growth factor-beta1 induces epithelial-to-mesenchymal transition and apoptosis via a cell cycle-dependent mechanism. Oncogene, 25, 7235-44. https://doi.org/10.1038/sj.onc.1209712

Cited by

  1. An Epigenetic Mechanism Underlying Doxorubicin Induced EMT in the Human BGC-823 Gastric Cancer Cell vol.15, pp.10, 2014, https://doi.org/10.7314/APJCP.2014.15.10.4271
  2. Nanoparticle Induced Oxidative Stress in Cancer Cells: Adding New Pieces to an Incomplete Jigsaw Puzzle vol.15, pp.12, 2014, https://doi.org/10.7314/APJCP.2014.15.12.4739
  3. Roles of Oxidative Stress in the Development and Progression of Breast Cancer vol.15, pp.12, 2014, https://doi.org/10.7314/APJCP.2014.15.12.4745
  4. Comparative Analysis of Oct4 in Different Histological Subtypes of Esophageal Squamous Cell Carcinomas in Different Clinical Conditions vol.15, pp.8, 2014, https://doi.org/10.7314/APJCP.2014.15.8.3519
  5. Related in Vitro Oxidant Stress vol.32, pp.4, 2014, https://doi.org/10.1080/10590501.2014.967061
  6. /HOCl-mediated enhancement of hepatocellular carcinoma cell tumorigenicity by suppressing cellular senescence vol.106, pp.5, 2015, https://doi.org/10.1111/cas.12632
  7. Enhancement of SOX-2 expression and ROS accumulation by culture of A172 glioblastoma cells under non-adherent culture conditions vol.34, pp.2, 2015, https://doi.org/10.3892/or.2015.4021
  8. Superoxide dismutase promotes the epithelial-mesenchymal transition of pancreatic cancer cells via activation of the H2O2/ERK/NF-κB axis vol.46, pp.6, 2015, https://doi.org/10.3892/ijo.2015.2938
  9. Zinc induces epithelial to mesenchymal transition in human lung cancer H460 cells via superoxide anion-dependent mechanism vol.16, pp.1, 2016, https://doi.org/10.1186/s12935-016-0323-4
  10. Plasma Circulating Cell-free Nuclear and Mitochondrial DNA as Potential Biomarkers in the Peripheral Blood of Breast Cancer Patients vol.16, pp.18, 2016, https://doi.org/10.7314/APJCP.2015.16.18.8299
  11. Tungsten Oxide Nanoplates; the Novelty in Targeting Metalloproteinase-7 Gene in Both Cervix and Colon Cancer Cells vol.180, pp.4, 2016, https://doi.org/10.1007/s12010-016-2120-x
  12. vol.2016, pp.1942-0994, 2016, https://doi.org/10.1155/2016/1908164
  13. The PI3K/AKT/c-MYC Axis Promotes the Acquisition of Cancer Stem-Like Features in Esophageal Squamous Cell Carcinoma vol.34, pp.8, 2016, https://doi.org/10.1002/stem.2395
  14. Residual Ammonium Persulfate in Nanoparticles Has Cytotoxic Effects on Cells through Epithelial-Mesenchymal Transition vol.7, pp.1, 2017, https://doi.org/10.1038/s41598-017-12328-0
  15. Effects of Chrysotile Exposure in Human Bronchial Epithelial Cells: Insights into the Pathogenic Mechanisms of Asbestos-Related Diseases vol.124, pp.6, 2016, https://doi.org/10.1289/ehp.1409627
  16. Phosphorylation of Sox2 at Threonine 116 is a Potential Marker to Identify a Subset of Breast Cancer Cells with High Tumorigenecity and Stem-Like Features vol.10, pp.2, 2018, https://doi.org/10.3390/cancers10020041
  17. Cancer Stem Cells: Emergent Nature of Tumor Emergency vol.9, pp.1664-8021, 2018, https://doi.org/10.3389/fgene.2018.00544
  18. Hypoxia promotes acquisition of aggressive phenotypes in human malignant mesothelioma vol.18, pp.1, 2018, https://doi.org/10.1186/s12885-018-4720-z
  19. Ultraviolet radiation oxidative stress affects eye health vol.11, pp.7, 2018, https://doi.org/10.1002/jbio.201700377
  20. Exosomes from asbestos-exposed cells modulate gene expression in mesothelial cells vol.32, pp.8, 2018, https://doi.org/10.1096/fj.201701291RR