Clinical & Experimental Metastasis

, Volume 25, Issue 6, pp 593–600 | Cite as

Matrix metalloproteinases stimulate epithelial-mesenchymal transition during tumor development

Research Paper


Matrix metalloproteinases (MMPs) are a family of more than 28 enzymes that were initially identified on the basis of their ability to cleave most elements of the extracellular matrix (ECM) but have subsequently been found to be upregulated in nearly every tumor type. As digestion of the ECM is essential for tumor invasion and metastasis, MMPs have been studied for their role in these later stages of tumor development. More recently, exposure to these enzymes has been found to impact cellular signaling pathways that stimulate cell growth at early stages of tumor progression. MMPs have also been found to cleave intracellular targets and so inducing mitotic abnormalities and genomic instability. Emerging evidence indicates that tumor-associated MMPs can also stimulate processes associated with epithelial-mesenchymal transition (EMT), a developmental process that is activated in tumor cells during cell invasion and metastasis. Investigations of potential therapeutic MMP inhibitors aimed at blocking the protumorigenic tissue alterations induced by MMPs have been complicated by the side effects associated with nonspecific inhibition of normal physiological processes; recent investigations have shown how delineation of the extracellular targets and intracellular signaling pathways by which MMP action on cancer cells can induce EMT provides insight into novel therapeutic targets. Here, we provide an overview of recent findings of MMP action in tumors and the mechanisms by which MMPs induce both phenotypic and genotypic alterations that facilitate tumor progression.


Epithelial-mesenchymal transition Matrix metalloproteinases Cancer Invasion 


  1. 1.
    Sieweke MH, Bissell MJ (1994) The tumor-promoting effect of wounding: a possible role for TGF-beta-induced stromal alterations. Crit Rev Oncog 5(2–3):297–311PubMedGoogle Scholar
  2. 2.
    Sternlicht MD, Werb Z (2001) How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 17:463–516PubMedCrossRefGoogle Scholar
  3. 3.
    Bissell MJ, Radisky D (2001) Putting tumours in context. Nat Rev Cancer 1(1):46–54PubMedCrossRefGoogle Scholar
  4. 4.
    Thiery JP, Sleeman JP (2006) Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 7(2):131–142PubMedCrossRefGoogle Scholar
  5. 5.
    Overall CM, Lopez-Otin C (2002) Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat Rev Cancer 2(9):657–672PubMedCrossRefGoogle Scholar
  6. 6.
    Matrisian LM (1994) Matrix metalloproteinase gene expression. Ann N Y Acad Sci 732:42–50PubMedCrossRefGoogle Scholar
  7. 7.
    Westermarck J, Kahari VM (1999) Regulation of matrix metalloproteinase expression in tumor invasion. Faseb J 13(8):781–792PubMedGoogle Scholar
  8. 8.
    Jones LE, Humphreys MJ, Campbell F et al (2004) Comprehensive analysis of matrix metalloproteinase and tissue inhibitor expression in pancreatic cancer: increased expression of matrix metalloproteinase-7 predicts poor survival. Clin Cancer Res 10(8):2832–2845PubMedCrossRefGoogle Scholar
  9. 9.
    Liu D, Nakano J, Ishikawa S et al (2007) Overexpression of matrix metalloproteinase-7 (MMP-7) correlates with tumor proliferation, and a poor prognosis in non-small cell lung cancer. Lung Cancer 58(3):384–391PubMedCrossRefGoogle Scholar
  10. 10.
    Morgia G, Falsaperla M, Malaponte G et al (2005) Matrix metalloproteinases as diagnostic (MMP-13) and prognostic (MMP-2, MMP-9) markers of prostate cancer. Urol Res 33(1):44–50PubMedCrossRefGoogle Scholar
  11. 11.
    Wu CY, Wu MS, Chiang EP et al (2007) Plasma matrix metalloproteinase-9 level is better than serum matrix metalloproteinase-9 level to predict gastric cancer evolution. Clin Cancer Res 13(7):2054–2060PubMedCrossRefGoogle Scholar
  12. 12.
    Mook OR, Frederiks WM, Van Noorden CJ (2004) The role of gelatinases in colorectal cancer progression and metastasis. Biochim Biophys Acta 1705(2):69–89PubMedGoogle Scholar
  13. 13.
    Somiari SB, Somiari RI, Heckman CM et al (2006) Circulating MMP2 and MMP9 in breast cancer—potential role in classification of patients into low risk, high risk, benign disease and breast cancer categories. Int J Cancer 119(6):1403–1411PubMedCrossRefGoogle Scholar
  14. 14.
    Tetu B, Brisson J, Wang CS et al (2006) The influence of MMP-14, TIMP-2 and MMP-2 expression on breast cancer prognosis. Breast Cancer Res 8(3):R28PubMedCrossRefGoogle Scholar
  15. 15.
    Yoshida H, Ishiko O, Sumi T et al (2001) Survivin, bcl-2 and matrix metalloproteinase-2 enhance progression of clear cell- and serous-type ovarian carcinomas. Int J Oncol 19(3):537–542PubMedGoogle Scholar
  16. 16.
    Katayama A, Bandoh N, Kishibe K et al (2004) Expressions of matrix metalloproteinases in early-stage oral squamous cell carcinoma as predictive indicators for tumor metastases and prognosis. Clin Cancer Res 10(2):634–640PubMedCrossRefGoogle Scholar
  17. 17.
    Kerkela E, Saarialho-Kere U (2003) Matrix metalloproteinases in tumor progression: focus on basal and squamous cell skin cancer. Exp Dermatol 12(2):109–125PubMedCrossRefGoogle Scholar
  18. 18.
    Illman SA, Lehti K, Keski-Oja J et al (2006) Epilysin (MMP-28) induces TGF-beta mediated epithelial to mesenchymal transition in lung carcinoma cells. J Cell Sci 119(Pt 18):3856–3865PubMedCrossRefGoogle Scholar
  19. 19.
    Radisky DC, Levy DD, Littlepage LE et al (2005) Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature 436(7047):123–127PubMedCrossRefGoogle Scholar
  20. 20.
    Lochter A, Sternlicht MD, Werb Z et al (1998) The significance of matrix metalloproteinases during early stages of tumor progression. Ann N Y Acad Sci 857:180–193PubMedCrossRefGoogle Scholar
  21. 21.
    Noel A, Boulay A, Kebers F et al (2000) Demonstration in vivo that stromelysin-3 functions through its proteolytic activity. Oncogene 19(12):1605–1612PubMedCrossRefGoogle Scholar
  22. 22.
    McGuire JK, Li Q, Parks WC (2003) Matrilysin (matrix metalloproteinase-7) mediates E-cadherin ectodomain shedding in injured lung epithelium. Am J Pathol 162(6):1831–1843PubMedGoogle Scholar
  23. 23.
    Song W, Jackson K, McGuire PG (2000) Degradation of type IV collagen by matrix metalloproteinases is an important step in the epithelial-mesenchymal transformation of the endocardial cushions. Dev Biol 227(2):606–617PubMedCrossRefGoogle Scholar
  24. 24.
    Karsdal MA, Larsen L, Engsig MT et al (2002) Matrix metalloproteinase-dependent activation of latent transforming growth factor-beta controls the conversion of osteoblasts into osteocytes by blocking osteoblast apoptosis. J Biol Chem 277(46):44061–44067PubMedCrossRefGoogle Scholar
  25. 25.
    Iida J, McCarthy JB (2007) Expression of collagenase-1 (MMP-1) promotes melanoma growth through the generation of active transforming growth factor-beta. Melanoma Res 17(4):205–213PubMedCrossRefGoogle Scholar
  26. 26.
    Yu Q, Stamenkovic I (2000) Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev 14(2):163–176PubMedGoogle Scholar
  27. 27.
    Yu WH, Woessner JF Jr, McNeish JD et al (2002) CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling. Genes Dev 16(3):307–323PubMedCrossRefGoogle Scholar
  28. 28.
    Cheng K, Xie G, Raufman JP (2007) Matrix metalloproteinase-7-catalyzed release of HB-EGF mediates deoxycholyltaurine-induced proliferation of a human colon cancer cell line. Biochem Pharmacol 73(7):1001–1012PubMedCrossRefGoogle Scholar
  29. 29.
    Manes S, Llorente M, Lacalle RA et al (1999) The matrix metalloproteinase-9 regulates the insulin-like growth factor-triggered autocrine response in DU-145 carcinoma cells. J Biol Chem 274(11):6935–6945PubMedCrossRefGoogle Scholar
  30. 30.
    Shubayev VI, Myers RR (2000) Upregulation and interaction of TNFalpha and gelatinases A and B in painful peripheral nerve injury. Brain Res 855(1):83–89PubMedCrossRefGoogle Scholar
  31. 31.
    Ito A, Mukaiyama A, Itoh Y et al (1996) Degradation of interleukin 1beta by matrix metalloproteinases. J Biol Chem 271(25):14657–14660PubMedCrossRefGoogle Scholar
  32. 32.
    Fishman DA, Bafetti LM, Stack MS (1996) Membrane-type matrix metalloproteinase expression and matrix metalloproteinase-2 activation in primary human ovarian epithelial carcinoma cells. Invasion Metastasis 16(3):150–159PubMedGoogle Scholar
  33. 33.
    Du B, Wang P, Guo X et al (1999) Expression of membrane type 1-matrix metalloproteinase in laryngeal carcinoma. Pathol Oncol Res 5(3):214–217PubMedCrossRefGoogle Scholar
  34. 34.
    Uchibori M, Nishida Y, Nagasaka T et al (2006) Increased expression of membrane-type matrix metalloproteinase-1 is correlated with poor prognosis in patients with osteosarcoma. Int J Oncol 28(1):33–42PubMedGoogle Scholar
  35. 35.
    Jiang WG, Davies G, Martin TA et al (2006) Expression of membrane type-1 matrix metalloproteinase, MT1-MMP in human breast cancer and its impact on invasiveness of breast cancer cells. Int J Mol Med 17(4):583–590PubMedGoogle Scholar
  36. 36.
    Sounni NE, Noel A (2005) Membrane type-matrix metalloproteinases and tumor progression. Biochimie 87(3–4):329–342PubMedCrossRefGoogle Scholar
  37. 37.
    Tam EM, Morrison CJ, Wu YI et al (2004) Membrane protease proteomics: Isotope-coded affinity tag MS identification of undescribed MT1-matrix metalloproteinase substrates. Proc Natl Acad Sci USA 101(18):6917–6922PubMedCrossRefGoogle Scholar
  38. 38.
    Gilles C, Polette M, Seiki M et al (1997) Implication of collagen type I-induced membrane-type 1-matrix metalloproteinase expression and matrix metalloproteinase-2 activation in the metastatic progression of breast carcinoma. Lab Invest 76(5):651–660PubMedGoogle Scholar
  39. 39.
    Ha HY, Moon HB, Nam MS et al (2001) Overexpression of membrane-type matrix metalloproteinase-1 gene induces mammary gland abnormalities and adenocarcinoma in transgenic mice. Cancer Res 61(3):984–990PubMedGoogle Scholar
  40. 40.
    Masson R, Lefebvre O, Noel A et al (1998) In vivo evidence that the stromelysin-3 metalloproteinase contributes in a paracrine manner to epithelial cell malignancy. J Cell Biol 140(6):1535–1541PubMedCrossRefGoogle Scholar
  41. 41.
    Mudgett JS, Hutchinson NI, Chartrain NA et al (1998) Susceptibility of stromelysin 1-deficient mice to collagen-induced arthritis and cartilage destruction. Arthritis Rheum 41(1):110–121PubMedCrossRefGoogle Scholar
  42. 42.
    Vu TH, Shipley JM, Bergers G et al (1998) MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell 93(3):411–422PubMedCrossRefGoogle Scholar
  43. 43.
    Itoh T, Tanioka M, Matsuda H et al (1999) Experimental metastasis is suppressed in MMP-9-deficient mice. Clin Exp Metastasis 17(2):177–181PubMedCrossRefGoogle Scholar
  44. 44.
    Holmbeck K, Bianco P, Caterina J et al (1999) MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 99(1):81–921PubMedCrossRefGoogle Scholar
  45. 45.
    Wolf K, Wu YI, Liu Y et al (2007) Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. Nat Cell Biol 9(8):893–904PubMedCrossRefGoogle Scholar
  46. 46.
    Hotary KB, Allen ED, Brooks PC et al (2003) Membrane type I matrix metalloproteinase usurps tumor growth control imposed by the three-dimensional extracellular matrix. Cell 114(1):33–45PubMedCrossRefGoogle Scholar
  47. 47.
    Nabeshima K, Inoue T, Shimao Y et al (2002) Matrix metalloproteinases in tumor invasion: role for cell migration. Pathol Int 52(4):255–264PubMedCrossRefGoogle Scholar
  48. 48.
    Dumin JA, Dickeson SK, Stricker TP et al (2001) Pro-collagenase-1 (matrix metalloproteinase-1) binds the alpha(2)beta(1) integrin upon release from keratinocytes migrating on type I collagen. J Biol Chem 276(31):29368–29374PubMedCrossRefGoogle Scholar
  49. 49.
    Stefanidakis M, Ruohtula T, Borregaard N et al (2004) Intracellular and cell surface localization of a complex between alphaMbeta2 integrin and promatrix metalloproteinase-9 progelatinase in neutrophils. J Immunol 172(11):7060–7068PubMedGoogle Scholar
  50. 50.
    Nisato RE, Hosseini G, Sirrenberg C et al (2005) Dissecting the role of matrix metalloproteinases (MMP) and integrin alpha(v)beta3 in angiogenesis in vitro: absence of hemopexin C domain bioactivity, but membrane-type 1-MMP and alpha(v)beta3 are critical. Cancer Res 65(20):9377–9387PubMedCrossRefGoogle Scholar
  51. 51.
    Thomas GJ, Lewis MP, Hart IR et al (2001) AlphaVbeta6 integrin promotes invasion of squamous carcinoma cells through up-regulation of matrix metalloproteinase-9. Int J Cancer 92(5):641–650PubMedCrossRefGoogle Scholar
  52. 52.
    Hamidi S, Salo T, Kainulainen T et al (2000) Expression of alpha(v)beta6 integrin in oral leukoplakia. Br J Cancer 82(8):1433–1440PubMedGoogle Scholar
  53. 53.
    Impola U, Uitto VJ, Hietanen J et al (2004) Differential expression of matrilysin-1 (MMP-7), 92 kD gelatinase (MMP-9), and metalloelastase (MMP-12) in oral verrucous and squamous cell cancer. J Pathol 202(1):14–22PubMedCrossRefGoogle Scholar
  54. 54.
    Brooks PC, Stromblad S, Sanders LC et al (1996) Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Cell 85(5):683–693PubMedCrossRefGoogle Scholar
  55. 55.
    Ellerbroek SM, Fishman DA, Kearns AS et al (1999) Ovarian carcinoma regulation of matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase through beta1 integrin. Cancer Res 59(7):1635–1641PubMedGoogle Scholar
  56. 56.
    Symowicz J, Adley BP, Gleason KJ et al (2007) Engagement of collagen-binding integrins promotes matrix metalloproteinase-9-dependent E-cadherin ectodomain shedding in ovarian carcinoma cells. Cancer Res 67(5):2030–2039PubMedCrossRefGoogle Scholar
  57. 57.
    Ratnikov BI, Rozanov DV, Postnova TI et al (2002) An alternative processing of integrin alpha(v) subunit in tumor cells by membrane type-1 matrix metalloproteinase. J Biol Chem 277(9):7377–7385PubMedCrossRefGoogle Scholar
  58. 58.
    von Bredow DC, Nagle RB, Bowden GT et al (1997) Cleavage of beta 4 integrin by matrilysin. Exp Cell Res 236(1):341–345CrossRefGoogle Scholar
  59. 59.
    Murray D, Morrin M, McDonnell S (2004) Increased invasion and expression of MMP-9 in human colorectal cell lines by a CD44-dependent mechanism. Anticancer Res 24(2A):489–494PubMedGoogle Scholar
  60. 60.
    Thanakit V, Sampatanukul P, Ruangvejvorachai P et al (2005) The association of co-expression of CD44v4/MMP-9 with different nodal status in high-grade breast carcinoma patients. J Med Assoc Thai 88(Suppl 4):S30–S35PubMedGoogle Scholar
  61. 61.
    Gabison EE, Hoang-Xuan T, Mauviel A et al (2005) EMMPRIN/CD147, an MMP modulator in cancer, development and tissue repair. Biochimie 87(3–4):361–368PubMedCrossRefGoogle Scholar
  62. 62.
    Tang Y, Kesavan P, Nakada MT et al (2004) Tumor-stroma interaction: positive feedback regulation of extracellular matrix metalloproteinase inducer (EMMPRIN) expression and matrix metalloproteinase-dependent generation of soluble EMMPRIN. Mol Cancer Res 2(2):73–80PubMedGoogle Scholar
  63. 63.
    Thomasset N, Lochter A, Sympson CJ et al (1998) Expression of autoactivated stromelysin-1 in mammary glands of transgenic mice leads to a reactive stroma during early development. Am J Pathol 153(2):457–467PubMedGoogle Scholar
  64. 64.
    Lochter A, Galosy S, Muschler J et al (1997) Matrix metalloproteinase stromelysin-1 triggers a cascade of molecular alterations that leads to stable epithelial-to-mesenchymal conversion and a premalignant phenotype in mammary epithelial cells. J Cell Biol 139(7):1861–1872PubMedCrossRefGoogle Scholar
  65. 65.
    Bergers G, Coussens LM (2000) Extrinsic regulators of epithelial tumor progression: metalloproteinases. Curr Opin Genet Dev 10(1):120–127PubMedCrossRefGoogle Scholar
  66. 66.
    Lee KH, Choi EY, Hyun MS et al (2007) Association of extracellular cleavage of E-cadherin mediated by MMP-7 with HGF-induced in vitro invasion in human stomach cancer cells. Eur Surg Res 39(4):208–215PubMedCrossRefGoogle Scholar
  67. 67.
    Covington MD, Burghardt RC, Parrish AR (2006) Ischemia-induced cleavage of cadherins in NRK cells requires MT1-MMP (MMP-14). Am J Physiol Renal Physiol 290(1):F43–F51PubMedCrossRefGoogle Scholar
  68. 68.
    Mei JM, Borchert GL, Donald SP et al (2002) Matrix metalloproteinase(s) mediate(s) NO-induced dissociation of beta-catenin from membrane bound E-cadherin and formation of nuclear beta-catenin/LEF-1 complex. Carcinogenesis 23(12):2119–2122PubMedCrossRefGoogle Scholar
  69. 69.
    Golubkov VS, Strongin AY (2007) Proteolysis-driven oncogenesis. Cell Cycle 6(2):147–150PubMedGoogle Scholar
  70. 70.
    Golubkov VS, Chekanov AV, Savinov AY et al (2006) Membrane type-1 matrix metalloproteinase confers aneuploidy and tumorigenicity on mammary epithelial cells. Cancer Res 66(21):10460–10465PubMedCrossRefGoogle Scholar
  71. 71.
    Golubkov VS, Chekanov AV, Doxsey SJ et al (2005) Centrosomal pericentrin is a direct cleavage target of membrane type-1 matrix metalloproteinase in humans but not in mice: potential implications for tumorigenesis. J Biol Chem 280(51):42237–42241PubMedCrossRefGoogle Scholar
  72. 72.
    Si-Tayeb K, Monvoisin A, Mazzocco C et al (2006) Matrix metalloproteinase 3 is present in the cell nucleus and is involved in apoptosis. Am J Pathol 169(4):1390–1401PubMedCrossRefGoogle Scholar
  73. 73.
    Limb GA, Matter K, Murphy G et al (2005) Matrix metalloproteinase-1 associates with intracellular organelles and confers resistance to lamin A/C degradation during apoptosis. Am J Pathol 166(5):1555–1563PubMedGoogle Scholar
  74. 74.
    Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2(3):161–174PubMedCrossRefGoogle Scholar
  75. 75.
    Sillanpaa S, Anttila M, Voutilainen K et al (2007) Prognostic significance of matrix metalloproteinase-9 (MMP-9) in epithelial ovarian cancer. Gynecol Oncol 104(2):296–303PubMedCrossRefGoogle Scholar
  76. 76.
    Zhang Q, Chen X, Zhou J et al (2006) CD147, MMP-2, MMP-9 and MVD-CD34 are significant predictors of recurrence after liver transplantation in hepatocellular carcinoma patients. Cancer Biol Ther 5(7):808–814PubMedCrossRefGoogle Scholar
  77. 77.
    Cardillo MR, Di Silverio F, Gentile V (2006) Quantitative immunohistochemical and in situ hybridization analysis of metalloproteinases in prostate cancer. Anticancer Res 26(2A):973–982PubMedGoogle Scholar
  78. 78.
    Ohtani H, Motohashi H, Sato H et al (1996) Dual over-expression pattern of membrane-type metalloproteinase-1 in cancer and stromal cells in human gastrointestinal carcinoma revealed by in situ hybridization and immunoelectron microscopy. Int J Cancer 68(5):565–570PubMedCrossRefGoogle Scholar
  79. 79.
    McCawley LJ, Crawford HC, King LE Jr et al (2004) A protective role for matrix metalloproteinase-3 in squamous cell carcinoma. Cancer Res 64(19):6965–6972PubMedCrossRefGoogle Scholar
  80. 80.
    Owen JL, Iragavarapu-Charyulu V, Gunja-Smith Z et al (2003) Up-regulation of matrix metalloproteinase-9 in T lymphocytes of mammary tumor bearers: role of vascular endothelial growth factor. J Immunol 171(8):4340–4351PubMedGoogle Scholar
  81. 81.
    Coussens LM, Tinkle CL, Hanahan D et al (2000) MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 103(3):481–490PubMedCrossRefGoogle Scholar
  82. 82.
    Tse JC, Kalluri R (2007) Mechanisms of metastasis: epithelial-to-mesenchymal transition and contribution of tumor microenvironment. J Cell Biochem 101(4):816–829PubMedCrossRefGoogle Scholar
  83. 83.
    Sternlicht MD, Lochter A, Sympson CJ et al (1999) The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell 98(2):137–146PubMedCrossRefGoogle Scholar
  84. 84.
    Sympson CJ, Bissell MJ, Werb Z (1995) Mammary gland tumor formation in transgenic mice overexpressing stromelysin-1. Semin Cancer Biol 6(3):159–163PubMedCrossRefGoogle Scholar
  85. 85.
    Lochter A, Srebrow A, Sympson CJ et al (1997) Misregulation of stromelysin-1 expression in mouse mammary tumor cells accompanies acquisition of stromelysin-1-dependent invasive properties. J Biol Chem 272(8):5007–5015PubMedCrossRefGoogle Scholar
  86. 86.
    Jordan P, Brazao R, Boavida MG et al (1999) Cloning of a novel human Rac1b splice variant with increased expression in colorectal tumors. Oncogene 18(48):6835–6839PubMedCrossRefGoogle Scholar
  87. 87.
    Schnelzer A, Prechtel D, Knaus U et al (2000) Rac1 in human breast cancer: overexpression, mutation analysis, and characterization of a new isoform, Rac1b. Oncogene 19(26):3013–3020PubMedCrossRefGoogle Scholar
  88. 88.
    Singh A, Karnoub AE, Palmby TR et al (2004) Rac1b, a tumor associated, constitutively active Rac1 splice variant, promotes cellular transformation. Oncogene 23(58):9369–9380PubMedCrossRefGoogle Scholar
  89. 89.
    Feig DI, Reid TM, Loeb LA (1994) Reactive oxygen species in tumorigenesis. Cancer Res 54(7 Suppl):1890s–1894sPubMedGoogle Scholar
  90. 90.
    Dong R, Wang Q, He XL et al (2007) Role of nuclear factor kappa B and reactive oxygen species in the tumor necrosis factor-a-induced epithelial-mesenchymal transition of MCF-7 cells. Braz J Med Biol Res 40(8):1071–1078PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  1. 1.Mayo Clinic Cancer CenterJacksonvilleUSA

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