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Vimentin and Epithelial-Mesenchymal Transition in Human Breast Cancer – Observations in vitro and in vivo

Kokkinos M.I.a · Wafai R.a · Wong M.K.a · Newgreen D.F.b · Thompson E.W.a, c · Waltham M.a, c

Author affiliations

aDepartment of Surgery, St. Vincent’s Hospital, University of Melbourne, bEmbryology Laboratory, Murdoch Children’s Research Institute, Royal Children’s Hospital, and cInvasion and Metastasis Unit, St. Vincent’s Institute of Medical Research, Victorian Breast Cancer Research Consortium, Melbourne, Australia

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Cells Tissues Organs 2007;185:191–203

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Article / Publication Details

First-Page Preview
Abstract of Paper

Received: May 24, 2006
Accepted: February 18, 2007
Published online: June 25, 2007
Issue release date: June 2007

Number of Print Pages: 13
Number of Figures: 7
Number of Tables: 2

ISSN: 1422-6405 (Print)
eISSN: 1422-6421 (Online)

For additional information: https://www.karger.com/CTO

Abstract

Breast cancer is a highly prevalent disease among women worldwide. While the expression of certain proteins within these tumours is used for prognosis and selection of therapies, there is a continuing need for additional markers to be identified. A considerable amount of current literature, based predominantly on cell culture systems, suggests that a major mechanism responsible for the progression of breast cancer is due to tumour cells losing their epithelial features and gaining mesenchymal properties. These events are proposed to be very similar to the epithelial-mesenchymal transition (EMT) process that has been well characterised in embryonic development. For the developmental and putative cancer EMT, the cell intermediate filament status changes from a keratin-rich network which connects to adherens junctions and hemidesmosomes, to a vimentin-rich network connecting to focal adhesions. This review summarises observations of vimentin expression in breast cancer model systems, and discusses the potential role of EMT in human breast cancer progression, and the prognostic usefulness of vimentin expression.

© 2007 S. Karger AG, Basel


References

  1. Ackland, M.L., D.F. Newgreen, M. Fridman, M.C. Waltham, A. Arvanitis, J. Minichiello, J.T. Price, E.W. Thompson (2003) Epidermal growth factor-induced epithelio-mesenchymal transition in human breast carcinoma cells. Lab Invest 83: 435–448.
  2. Addis, B.J., B. Corrin (1985) Pulmonary blastoma, carcinosarcoma and spindle-cell carcinoma: an immunohistochemical study of keratin intermediate filaments. J Pathol 147: 291–301.
  3. Badwaik, N.K., J.J. Rasweiler, 4th, F. Muradali (1998) Co-expression of cytokeratins and vimentin by highly invasive trophoblast in the white-winged vampire bat, Diaemus youngi, and the black mastiff bat, Molossus ater, with observations on intermediate filament proteins in the decidua and intraplacental trophoblast. J Reprod Fertil 114: 307–325.
  4. Bakin, A.V., A.K. Tomlinson, N.A. Bhowmick, H.L. Moses, C.L. Arteaga (2000) Phosphatidylinositol 3-kinase function is required for transforming growth factor beta-mediated epithelial to mesenchymal transition and cell migration. J Biol Chem 275: 36803–36810.
  5. Capetanaki, Y., S. Smith, J.P. Heath (1989) Overexpression of the vimentin gene in transgenic mice inhibits normal lens cell differentiation. J Cell Biol 109: 1653–1664.
  6. Carter, V., B.K. Shenton, B. Jaques, D. Turner, D. Talbot, A. Gupta, C.E. Chapman, C.J. Matthews, G. Cavanagh (2005) Vimentin antibodies: a non-HLA antibody as a potential risk factor in renal transplantation. Transplant Proc 37: 654–657.
  7. Condeelis, J., J.E. Segall (2003) Intravital imaging of cell movement in tumours. Nat Rev Cancer 3: 921–930.
  8. Devkota, B., M. Sasaki, M. Matsui, C. Amaya Montoya, Y.I. Miyake (2006) Alterations in the immunohistochemical localization patterns of alpha-smooth muscle actin (SMA) and vimentin in the postnatally developing bovine cryptorchid testis. J Reprod Dev 52: 329–334.
  9. Duband, J.L., F. Monier, M. Delannet, D. Newgreen (1995) Epithelium-mesenchyme transition during neural crest development. Acta Anat (Basel) 154: 63–78.
  10. Dumitrescu, R.G., I. Cotarla (2005) Understanding breast cancer risk – where do we stand in 2005? J Cell Mol Med 9: 208–221.
  11. Eckes, B., E. Colucci-Guyon, H. Smola, S. Nodder, C. Babinet, T. Krieg, P. Martin (2000) Impaired wound healing in embryonic and adult mice lacking vimentin. J Cell Sci 113(Pt 13): 2455–2462.
  12. Ehmann, U.K., J.T. DeVries, M.S. Chen, A.A. Adamos, R.C. Guzman, M.B. Omary (2003) An in vitro model of epithelial cell growth stimulation in the rodent mammary gland. Cell Prolif 36: 177–190.
  13. Eriksson, J.E., T. He, A.V. Trejo-Skalli, A.S. Harmala-Brasken, J. Hellman, Y.H. Chou, R.D. Goldman (2004) Specific in vivo phosphorylation sites determine the assembly dynamics of vimentin intermediate filaments. J Cell Sci 117: 919–932.
  14. Evans, R.M. (1998) Vimentin: the conundrum of the intermediate filament gene family. Bioessays 20: 79–86.
  15. Fitchett, J.E., E.D. Hay (1989) Medial edge epithelium transforms to mesenchyme after embryonic palatal shelves fuse. Dev Biol 131: 455–474.
  16. Franke, W.W., C. Grund, C. Kuhn, B.W. Jackson, K. Illmensee (1982) Formation of cytoskeletal elements during mouse embryogenesis. III. Primary mesenchymal cells and the first appearance of vimentin filaments. Differentiation 23: 43–59.
  17. Galou, M., E. Colucci-Guyon, D. Ensergueix, J.L. Ridet, M. Gimenez y Ribotta, A. Privat, C. Babinet, P. Dupouey (1996) Disrupted glial fibrillary acidic protein network in astrocytes from vimentin knockout mice. J Cell Biol 133: 853–863.
  18. Galou, M., J. Gao, J. Humbert, M. Mericskay, Z. Li, D. Paulin, P. Vicart (1997) The importance of intermediate filaments in the adaptation of tissues to mechanical stress: evidence from gene knockout studies. Biol Cell 89: 85–97.
  19. Gavrilovic, J., G. Moens, J.P. Thiery, J. Jouanneau (1990) Expression of transfected transforming growth factor alpha induces a motile fibroblast-like phenotype with extracellular matrix-degrading potential in a rat bladder carcinoma cell line. Cell Regul 1: 1003–1014.
  20. Gilles, C., E.W. Thompson (1996) The epithelial to mesenchymal transition and metastatic progression in carcinoma. Breast J 2: 83–96.
    External Resources
  21. Gilles, C., M. Polette, J. Zahm, J. Tournier, L. Volders, J. Foidart, P. Birembaut (1999) Vimentin contributes to human mammary epithelial cell migration. J Cell Sci 112: 4615–4625.
  22. Gilles, C., M. Polette, M. Mestdagt, B. Nawrocki-Raby, P. Ruggeri, P. Birembaut, J.M. Foidart (2003) Transactivation of vimentin by beta-catenin in human breast cancer cells. Cancer Res 63: 2658–2664.
  23. Gilles, C., D. Newgreen, H. Sato, E.W. Thompson (2004) Matrix metalloproteases and epithelial-to mesenchymal transition: implications for carcinoma metastasis; in Savagner, P. (ed): Rise and Fall of Epithelial Phenotype. Georgetown, Landes Bioscience Publishers, pp 297–315. www.eurekah.com.
  24. Giunciuglio, D., M. Culty, G. Fassina, L. Masiello, A. Melchiori, G. Paglialunga, G. Arand, F. Ciardiello, F. Basolo, E.W. Thompson, et al. (1995) Invasive phenotype of MCF10A cells overexpressing c-Ha-ras and c-erbB-2 oncogenes. Int J Cancer 63: 815–822.
  25. Grunert, S., M. Jechlinger, H. Beug (2003) Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat Rev Mol Cell Biol 4: 657–665.
  26. Haigh, T., C. Chen, C.J. Jones, J.D. Aplin (1999) Studies of mesenchymal cells from 1st trimester human placenta: expression of cytokeratin outside the trophoblast lineage. Placenta 20: 615–625.
  27. Heatley, M.K., P. Ewings, W. Odling Smee, P. Maxwell, P.G. Toner (2002) Vimentin expression does not assist in predicting survival in ductal carcinoma of the breast. Pathology 34: 230–232.
  28. Helfand, B.T., L. Chang, R.D. Goldman (2004) Intermediate filaments are dynamic and motile elements of cellular architecture. J Cell Sci 117: 133–141.
  29. Hendrix, M.J., E.A. Seftor, R.E. Seftor, K.T. Trevor (1997) Experimental co-expression of vimentin and keratin intermediate filaments in human breast cancer cells results in phenotypic interconversion and increased invasive behavior. Am J Pathol 150: 483–495.
  30. Holwell, T.A., S.C. Schweitzer, R.M. Evans (1997) Tetracycline regulated expression of vimentin in fibroblasts derived from vimentin null mice. J Cell Sci 110(Pt 16): 1947–1956.
  31. Huber, M.A., N. Azoitei, B. Baumann, S. Grunert, A. Sommer, H. Pehamberger, N. Kraut, H. Beug, T. Wirth (2004) NF-κB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. J Clin Invest 114: 569–581.
  32. Kaufmann, O., T. Deidesheimer, M. Muehlenberg, P. Deicke, M. Dietel (1996) Immunohistochemical differentiation of metastatic breast carcinomas from metastatic adenocarcinomas of other common primary sites. Histopathology 29: 233–240.
  33. Korsching, E., J. Packeisen, C. Liedtke, D. Hungermann, P. Wulfing, P.J. van Diest, B. Brandt, W. Boecker, H. Buerger (2005) The origin of vimentin expression in invasive breast cancer: epithelial-mesenchymal transition, myoepithelial histogenesis or histogenesis from progenitor cells with bilinear differentiation potential? J Pathol 206: 451–457.
  34. Lafleur, M.A., A.F. Drew, E.L. de Sousa, T. Blick, M. Bills, E.C. Walker, E.D. Williams, M. Waltham, E.W. Thompson (2005) Upregulation of matrix metalloproteinases (MMPs) in breast cancer xenografts: A major induction of stromal MMP-13. Int J Cancer 114: 544–554.
  35. Larsson, A., U. Wilhelmsson, M. Pekna, M. Pekny (2004) Increased cell proliferation and neurogenesis in the hippocampal dentate gyrus of old GFAP(–/–)Vim(–/–) mice. Neurochem Res 29: 2069–2073.
  36. Lee, J.M., S. Dedhar, R. Kalluri, E.W. Thompson (2006) The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol 172: 973–981.
  37. Lochter, A., Z. Werb, M.J. Bissell (1999) Transcriptional regulation of stromelysin-1 gene expression is altered during progression of mouse mammary epithelial cells from functionally normal to malignant. Matrix Biol 18: 455–467.
  38. Michalczyk, A., R.W. Brown, J.P. Collins, M.L. Ackland (2001) Lactation affects expression of intermediate filaments in human breast epithelium. Differentiation 67: 41–49.
  39. Miettinen, P.J., R. Ebner, A.R. Lopez, R. Derynck (1994) TGF-beta induced transdifferentiation of mammary epithelial cells to mesenchymal cells: involvement of type I receptors. J Cell Biol 127: 2021–2036.
  40. Moisan, E., D. Girard (2006) Cell surface expression of intermediate filament proteins vimentin and lamin B1 in human neutrophil spontaneous apoptosis. J Leukoc Biol 79: 489–498.
  41. Nagaraja, G.M., M. Othman, B.P. Fox, R. Alsaber, C.M. Pellegrino, Y. Zeng, R. Khanna, P. Tamburini, A. Swaroop, R.P. Kandpal (2006) Gene expression signatures and biomarkers of noninvasive and invasive breast cancer cells: comprehensive profiles by representational difference analysis, microarrays and proteomics. Oncogene 25: 2328–2338.
  42. Nieman, M.T., R.S. Prudoff, K.R. Johnson, M.J. Wheelock (1999) N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression. J Cell Biol 147: 631–644.
  43. Page, M. (1989) Changing patterns of cytokeratins and vimentin in the early chick embryo. Development 105: 97–107.
  44. Perou, C.M., T. Sorlie, M.B. Eisen, M. van de Rijn, S.S. Jeffrey, C.A. Rees, J.R. Pollack, D.T. Ross, H. Johnsen, L.A. Akslen, O. Fluge, A. Pergamenschikov, C. Williams, S.X. Zhu, P.E. Lonning, A.L. Borresen-Dale, P.O. Brown, D. Botstein (2000) Molecular portraits of human breast tumours. Nature 406: 747–752.
  45. Petersen, O.W., H. Lind Nielsen, T. Gudjonsson, R. Villadsen, L. Ronnov-Jessen, M.J. Bissell (2001) The plasticity of human breast carcinoma cells is more than epithelial to mesenchymal conversion. Breast Cancer Res 3: 213–217.
  46. Rae, J.M., M.D. Johnson, J.O. Scheys, K.E. Cordero, J.M. Larios, M.E. Lippman (2005) GREB 1 is a critical regulator of hormone dependent breast cancer growth. Breast Cancer Res Treat 92: 141–149.
  47. Rakha, E.A., D.A. El-Rehim, C. Paish, A.R. Green, A.H. Lee, J.F. Robertson, R.W. Blamey, D. Macmillan, I.O. Ellis (2006) Basal phenotype identifies a poor prognostic subgroup of breast cancer of clinical importance. Eur J Cancer 42: 3149–3156.
  48. Rastaldi, M.P., F. Ferrario, L. Giardino, G. Dell’Antonio, C. Grillo, P. Grillo, F. Strutz, G.A. Muller, G. Colasanti, G. D’Amico (2002) Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies. Kidney Int 62: 137–146.
  49. Reis-Filho, J.S. (2005) Re: Korsching et al. The origin of vimentin expression in invasive breast cancer: epithelial-mesenchymal transition, myoepithelial histogenesis or histogenesis from progenitor cells with bilinear differentiation potential? J Pathol 2005;206:451–457. J Pathol 207: 367–369; author reply 370–361.
  50. Runembert, I., S. Couette, P. Federici, E. Colucci-Guyon, C. Babinet, P. Briand, G. Friedlander, F. Terzi (2004) Recovery of Na-glucose cotransport activity after renal ischemia is impaired in mice lacking vimentin. Am J Physiol Renal Physiol 287: F960–F968.
  51. Sarria, A.J., S.R. Panini, R.M. Evans (1992) A functional role for vimentin intermediate filaments in the metabolism of lipoprotein-derived cholesterol in human SW-13 cells. J Biol Chem 267: 19455–19463.
  52. Schietke, R., D. Brohl, T. Wedig, N. Mucke, H. Herrmann, T.M. Magin (2006) Mutations in vimentin disrupt the cytoskeleton in fibroblasts and delay execution of apoptosis. Eur J Cell Biol 85: 1–10.
  53. Seshadri, R., W.A. Raymond, A.S. Leong, D.J. Horsfall, K. McCaul (1996) Vimentin expression is not associated with poor prognosis in breast cancer. Int J Cancer 67: 353–356.
  54. Sternlicht, M.D., A. Lochter, C.J. Sympson, B. Huey, J.P. Rougier, J.W. Gray, D. Pinkel, M.J. Bissell, Z. Werb (1999) The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell 98: 137–146.
  55. Strizzi, L., C. Bianco, N. Normanno, M. Seno, C. Wechselberger, B. Wallace-Jones, N.I. Khan, M. Hirota, Y. Sun, M. Sanicola, D.S. Salomon (2004) Epithelial mesenchymal transition is a characteristic of hyperplasias and tumors in mammary gland from MMTV-Cripto-1 transgenic mice. J Cell Physiol 201: 266–276.
  56. Thiery, J.P., J.P. Sleeman (2006) Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 7: 131–142.
  57. Thompson, E.W., S. Paik, N. Brunner, C.L. Sommers, G. Zugmaier, R. Clarke, T.B. Shima, J. Torri, S. Donahue, M.E. Lippman, et al. (1992) Association of increased basement membrane invasiveness with absence of estrogen receptor and expression of vimentin in human breast cancer cell lines. J Cell Physiol 150: 534–544.
  58. Thompson, E.W., J. Torri, M. Sabol, C.L. Sommers, S. Byers, E.M. Valverius, G.R. Martin, M.E. Lippman, M.R. Stampfer, R.B. Dickson (1994) Oncogene-induced basement membrane invasiveness in human mammary epithelial cells. Clin Exp Metastasis 12: 181–194.
  59. Thompson, E.W., D.F. Newgreen, D. Tarin (2005) Carcinoma invasion and metastasis: a role for epithelial-mesenchymal transition? Cancer Res 65: 5991–5995; discussion 5995.
  60. Vincent-Salomon, A., J.P. Thiery (2003) Host microenvironment in breast cancer development: epithelial-mesenchymal transition in breast cancer development. Breast Cancer Res 5: 101–106.
  61. Walter, I., S. Schonkypl (2006) Extracellular matrix components and matrix degrading enzymes in the feline placenta during gestation. Placenta 27: 291–306.
  62. Ward, K.R., K.X. Zhang, A.M. Somasiri, C.D. Roskelley, J.W. Schrader (2004) Expression of activated M-Ras in a murine mammary epithelial cell line induces epithelial-mesenchymal transition and tumorigenesis. Oncogene 23: 1187–1196.
  63. Willipinski-Stapelfeldt, B., S. Riethdorf, V. Assmann, U. Woelfle, T. Rau, G. Sauter, J. Heukeshoven, K. Pantel (2005) Changes in cytoskeletal protein composition indicative of an epithelial-mesenchymal transition in human micrometastatic and primary breast carcinoma cells. Clin Cancer Res 11: 8006–8014.
  64. Willis, B.C., J.M. Liebler, K. Luby-Phelps, A.G. Nicholson, E.D. Crandall, R.M. du Bois, Z. Borok (2005) Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-β1: potential role in idiopathic pulmonary fibrosis. Am J Pathol 166: 1321–1332.
  65. Yang, J., Y. Liu (2001) Dissection of key events in tubular epithelial to myofibroblast transition and its implications in renal interstitial fibrosis. Am J Pathol 159: 1465–1475.
  66. Zajchowski, D.A., M.F. Bartholdi, Y. Gong, L. Webster, H.L. Liu, A. Munishkin, C. Beauheim, S. Harvey, S.P. Ethier, P.H. Johnson (2001) Identification of gene expression profiles that predict the aggressive behavior of breast cancer cells. Cancer Res 61: 5168–5178.

Article / Publication Details

First-Page Preview
Abstract of Paper

Received: May 24, 2006
Accepted: February 18, 2007
Published online: June 25, 2007
Issue release date: June 2007

Number of Print Pages: 13
Number of Figures: 7
Number of Tables: 2

ISSN: 1422-6405 (Print)
eISSN: 1422-6421 (Online)

For additional information: https://www.karger.com/CTO


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