Breast Cancer Research and Treatment

, Volume 51, Issue 1, pp 57–69 | Cite as

Migration of breast epithelial cells on Laminin-5: differential role of integrins in normal and transformed cell types

  • George E. Plopper
  • Susan Z. Domanico
  • Vincenzo Cirulli
  • William B. Kiosses
  • Vito Quaranta
Article

Abstract

We examined the role of Laminin-5 (Ln-5) an extracellular matrix component of breast gland basement membrane, in supporting migration of normal (HUMEC), immortalized (MCF-10A), and malignant breast epithelial cells that exhibit different degrees of metastatic potential (MDA-MB-435>MDA-MB-231>MCF-7). HUMEC, MCF-10A, and MCF-7 cells all adhered to purified Ln-5 through the α3β1 integrin receptor in adhesion assays. However, HUMEC and MCF-10A cells remained statically adherent, while MCF-7 cells migrated on Ln-5 in Transwell and colloidal gold displacement assays. Anti-α3 integrin antibodies blocked migration of MCF-7 cells on Ln-5. MDA-MB-231 and MDA-MB-435 cells bound and migrated on Ln-5 through a β1 integrin receptor that is insensitive to antibodies that block the function of α1, α2, α3, α4, α5, α6, and αV integrin subunits. Migration of all cell types tested was blocked by CM6, a monoclonal antibody directed to a cell adhesion site on the α3 chain of Ln-5. Thus, Ln-5 may play an important role in regulating adhesion and migration in normal and transformed breast epithelium. Our results indicate that the type of integrin utilized by breast cells to interact with Ln-5, as well as its functional state, may determine whether cells will be statically adherent or migratory on Ln-5.

breast neoplasms extracellular matrix haptotaxis integrins laminins 

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References

  1. 1.
    Hynes RO: Integrins: Versatility, modulation and signaling in cell adhesion. Cell 69: 11–25, 1992Google Scholar
  2. 2.
    Craig SW, Johnson RP: Assembly of focal adhesions: progress, paradigms, and portents. Curr Opin Cell Biol 8: 74–85, 1996Google Scholar
  3. 3.
    Schwartz MA, Schaller MA, Ginsberg MH: Integrins: Emerging paradigms of signal transduction. Annu Rev Cell Dev Biol 11: 549–599, 1995Google Scholar
  4. 4.
    Lauffenburger DA, Horwitz AF: Cell migration: a physically integrated molecular process. [Review], Cell 84: 359–369, 1996Google Scholar
  5. 5.
    Huttenlocher A, Sandborg RR, Horwitz AF: Adhesion in cell migration. [Review]. Curr Opin Cell Biol 7: 697–706, 1995Google Scholar
  6. 6.
    Magro G, Lanzafame S, Colombatti A: Immunohistochemical staining patterns of type VI collagen in the normal, hyperplastic, and neoplastic adult male breast. Pathologica 86: 142–145, 1994Google Scholar
  7. 7.
    Christensen L: The distribution of fibroncctin, laminin and tetranectin in human breast cancer with special attention to the extracellular matrix. [Review]. APMIS Suppl 26: 1–39, 1992Google Scholar
  8. 8.
    Coopman P, Verhasselt B, Bracke M, De Bruyne G, Castronovo V, Sobel M, Foidart JM, Van Roy F, Marcel M: Arrest of MCF-7 cell migration by laminin in vitro: possible mechanisms. Clin Exp Metastasis 9: 469–484, 1991Google Scholar
  9. 9.
    D'Ardonno AJ, Richman PI, Horton MA, Meaulay AE, Jordan S: Co-ordinate expression of the alpha-6 integrin laminin receptor sub-unit and laminin in breast cancer. J Pathol 165: 213–220, 1991Google Scholar
  10. 10.
    Yoshida T, Ishihara A, Hirokawa Y, Kusakabe M, Sakakura T: Tenasein in breast cancer development — is epithelial tenascin a marker for poor prognosis? [Review]. Cancer Lett 90: 65–73, 1995Google Scholar
  11. 11.
    Jaskiewiez K, Chasen MR, Robson SC: Differential expression of extracellular matrix proteins and integrins in hepatocellular carcinoma and chronic liver disease. Anticancer Res 13: 2229–2237, 1993Google Scholar
  12. 12.
    Shoji T, Kamiya T, Tsubura A, Hamada Y, Hatano T, Hioki K, Morii S: Tenascin staining positivity and the survival of patients with invasive breast carcinoma. J Surg Res 55: 295–297, 1993Google Scholar
  13. 13.
    Moch H, Torhorst J, Durmuller U, Feichter GE, Sauter G, Gudat F: Comparative analysis of the expression of tenasein and established prognostic factors in human breast cancer. Pathol Res Pract 189: 510–514, 1993Google Scholar
  14. 14.
    Narita T, Kawakami-Kimura N, Sato M, Matsuura N, Higashiyama S, Kannagi R: Alteration of integrins by heparin-binding EGF-like growth factor in human breast cancer cells. Oncology 53: 374–381, 1996Google Scholar
  15. 15.
    Gui GP, Wells CA, Yeomans P, Jordan SE, Vinson GP, Carpenter R: Integrin expression in breast cancer cytology: a novel predictor of axillary metastasis. Eur J Surg Oncol 22: 254–258, 1996Google Scholar
  16. 16.
    Tawil NJ, Gowri V, Djoneidi M, Nip J, Carbonetto S, Brodt P: Integrin alpha 3 beta 1 can promote adhesion and spreading of metastatic breast carcinoma cells on the lymph node stroma. Int J Cancer 66: 703–710, 1996Google Scholar
  17. 17.
    Shaw LM, Chao C, Wewer UM, Mercurio AM: Function of the integrin alpha 6 beta 1 in metastatic breast carcinoma cells assessed by expression of a dominant-negative receptor. Cancer Res 56: 959–963, 1996Google Scholar
  18. 18.
    Maemura M, Akiyama SK, Woods VL Jr, Dickson RB: Expression and ligand binding of alpha 2 beta 1 integrin on breast carcinoma cells. Clin Exp Metastasis 13: 223–235, 1995Google Scholar
  19. 19.
    Glukhova M, Koteliansky V, Sastre X, Thiery JP: Adhesion systems in normal breast and in invasive breast carcinoma. Am J Pathol 146: 706–716, 1995Google Scholar
  20. 20.
    Friedrichs K, Ruiz P, Franke F, Gille T, Terpe HJ, Imhof BA: High expression level of alpha 6 integrin in human breast carcinoma is correlated with reduced survival. Cancer Res 55: 901–906, 1995Google Scholar
  21. 21.
    Gui GP, Wells CA, Browne PD, Yeomans P, Jordan S, Puddefoot JR, Carpenter R: Integrin expression in primary breast cancer and its relation to axillary nodal status. Surgery 117: 102–108, 1995Google Scholar
  22. 22.
    Oda K, Itoh H, Utsunomiya H, Itoh J, Osamura RY, Tokuda Y, Kubota M: Bio-histochemical aspects of integrins (alpha 2 beta 1, alpha 6 beta 1) in invasive mammary carcinomas: an immunohistochemical study. Pathol Int 44: 435–441, 1994Google Scholar
  23. 23.
    Arihiro K, Inai K, Kurihara K, Takeda S, Khatun N, Kuroi K, Toge T: A role of VLA-6 laminin receptor in invasion of breast carcinoma. Acta Pathol Jpn 43: 662–669, 1993Google Scholar
  24. 24.
    Sager R, Anisowiez A, Neveu M, Liang P, Sotiropoulou G: Identification by differential display of alpha 6 integrin as a candidate tumor suppressor gene. Faseb J 7: 964–970, 1993Google Scholar
  25. 25.
    Jones JL, Critchley DR, Walker RA: Alteration of stromal protein and integrin expression in breast a marker of premalignant change. J Pathol 167: 399–406, 1992Google Scholar
  26. 26.
    Natali PG, Nicotra MR, Botti C, Mottolese M, Bigotti A, Segatto O: Changes in expression of alpha 6/beta 4 integrin heterodimer in primary and metastatic breast cancer. Br J Cancer 66: 318–322, 1992Google Scholar
  27. 27.
    Koukoulis GK, Virtanen I, Korhonen M, Laitinen L, Quaranta V, Gould VE: Immunohistochemical localization of integrins in the normal, hyperplastic and neoplastic breast: Correlation with their functions as receptor and cell adhesion molecules. Am J Pathol 139: 787–799, 1991Google Scholar
  28. 28.
    Soule HD, Maloney TM, Wolman SR, Peterson WD Jr, Brenz R, McGrath CMR, Pauley RJ, Jones RF, Brooks SC: Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Res 50: 6075–6086, 1990Google Scholar
  29. 29.
    Band V, Sager R: Distinctive traits of normal and tumor-derived human mammary epithelial cells expressed in a medium that supports long-term growth of both cell types. Proc Natl Acad Sci USA 86: 1249–1253, 1989Google Scholar
  30. 30.
    Gelmann EP, Thompson EW, Sommers CL: Invasive and metastatic properties of MCF-7 cells and rasH-transfected MCF-7 cell lines. Int J Cancer 50: 665–669, 1992Google Scholar
  31. 31.
    Price JE, Polyzos A, Zhang RD, Daniels LM: Tumorigenicity and metastasis of human breast carcinoma cell lines in nude mice. Cancer Res 50: 717–721, 1990Google Scholar
  32. 32.
    Zhang RD, Fidler IJ, Price JE: Relative malignant potential of human breast carcinoma cell lines established from pleural effusions and a brain metatasis. Invasion Metastasis 11: 204–215, 1991Google Scholar
  33. 33.
    Riddelle KS, Green KJ, Jones JCR: Formation of hemides-mosomes in vitro by a transformed rat bladder cell lines. J Cell Biol 112: 159–168, 1991Google Scholar
  34. 34.
    Lehmann M, Rabenandrasana C, Tamura RN, Lissitzky JC, Quaranta V, Pinchon J, Marvaldi J: A monoclonal antibody inhibits adhesion to fibronectin and vitronectin of a colon carcinoma cell line and recognizes the integrins αVβ3, αVβ5 and αVβ6. Cancer Res 54: 2102–2107, 1994Google Scholar
  35. 35.
    Plopper G, Falk-Marzillier J, Glaser S, Fitchmun M, Giannelli G, Romano T, Jones JCR, Quaranta V: Changes in expression in monoclonal antibody epitopes on laminin-5r induced by cell contact. J Cell Sci 109: 1965–1973, 1996Google Scholar
  36. 36.
    Gospodarowicz D: Preparation of extracellular matrices produceed by cultured bovine corneal endothelial cells and PF-HR-9 endodermal cells: Their use in cell culture. In: Barnes DW, Sirbasku DA, Stao GH (eds) Methods for Preparation of Media, Supplements and Substrata. Alan R. Liss, Inc., New York, 1984, pp 275–293Google Scholar
  37. 37.
    Albrecht-Buchler G: The phagokinetic tracks of 3T3 cells. Cell 11: 395–404, 1977Google Scholar
  38. 38.
    Tamura RN, Cooper HM, Collo G, Quaranta V: Cell-type specific integrin variants with alternative α chain cytoplasmic domains. Proc Natl Acad Sci USA 88: 10183–10187, 1991Google Scholar
  39. 39.
    Takada Y, Murphy E, Pil P, Chen C, Ginsberg MH, Hemler ME: Mulecular cloning and expression of the eDNA for alpha 3 subunit of human alpha 3 beta 1 (VLA-3), an integrin receptor for fibronectin laminin and collagen. J Cell Biol 115: 257–266, 1991Google Scholar
  40. 40.
    Quaranta V, Plopper GE: Integrins and laminins in tissue remodeling. Kidney Int 51: 1441–1446, 1997Google Scholar
  41. 41.
    Wayner EA, Carter WG, Piotrowiez RS, Kunicki TJ: The function of multiple extracellular matrix receptors in mediating cell adhesion to extracellular matrix: Preparation of monoclonal antibodies to the fibronectin receptor that specifically inhibit cell adhesion to fibronectin and react with platelet glycoproteins Ic-IIa. J Cell Biol 107: 1881–1891, 1989Google Scholar
  42. 42.
    Sonnenberg A, Janssen H, Hogervorst F, Calafat J, Hilgers J: A complex of platelet glycoproteins Ic and IIa identified by a rat monoclonal antibody. J Biol Chem 262: 10376–10383, 1987Google Scholar
  43. 43.
    Carter WG, Wayner EA, Bouchard TS, Kaur P: The role of integrins alpha 2 beta 1 and alpha 3 beta 1 in cell-cell and cell-substrate adhesion of human epidermal cells. J Cell Biol 110: 1387–1404, 1990Google Scholar
  44. 44.
    Giannelli G, Falk-Marzillier J, Schiraldi O, Stetler-Stevenson WG, Quaranta V: Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5. Science 277: 225–228, 1997Google Scholar
  45. 45.
    Mullen P, Ritchie A, Langdon SP, Miller WR: Effect of Matrigel on the tumorigenicity of human breast and ovarian carcinoma cell lines. Int J Cancer 67: 816–820, 1996Google Scholar
  46. 46.
    Noel A, Borey V, Bracke M, Gilles C, Bernard J, Birembaut P, Mareel M, Foidart JM: Heterotransplantation of primary and established human tumour cells in nude mice. Anticancer Res 15: 1–7, 1995Google Scholar
  47. 47.
    Bao L, Matsumura Y, Baban D, Sun Y, Tarin D: Effects of inoculation site and Matrigel on growth and metastasis of human breast cancer cells. Br J Cancer 70: 228–232, 1994Google Scholar
  48. 48.
    Mehta RR, Graves JM, Hart GD, Shilkaitis A, Das Gupta TK: Growth and metastasis of human breast carcinomas with Matrigel in athymic mice. Breast Cancer Res Treat 25: 65–71, 1993Google Scholar
  49. 49.
    Bae SN, Arand G, Azzam H, Pavasant P, Torrt J, Frandsen TL, Thompson EW: Molecular and cellular analysis of basement membrane invasion by human breast cancer cells in Matrigel-based in vitro assays. Breast Cancer Res Treat 24: 241–255, 1993Google Scholar
  50. 50.
    Lelievre S, Weaver VM, Bissell MJ: Extracellular matrix signaling from the cellular membrane skeleton to the nuclear skeleton: a model of gene regulation. [Review]. Recent Prog Horm Res 51: 417–432, 1996Google Scholar
  51. 51.
    Stahl S, Weitzman S, Jones JCR: The role of laminin-5 and its receptors in mammary epithelial cell branching morphogenesis. J Cell Sci 110: 55–63, 1997Google Scholar
  52. 52.
    Niessen CM, Hogervorst F, Jaspars LH, de Melker AA, Delwel GO, Kuikman I, Sonnenberg A: The alpha 6 beta 4 integrin is a receptor for both laminin and kalinin. Exp Cell Res 211: 360–367, 1994Google Scholar
  53. 53.
    Anbazhagan R, Bartkova J, Stamp G, Pignatelli M, Gusterson B: Expression of integrin subunits in the human infant breast correlates with morphogenesis and differentiation. J Pathol 176: 227–232, 1995Google Scholar
  54. 54.
    Xia Y, Gil SG, Carter WG: Anchorage mediated by integrin alpha 6 beta 4 to laminin 5 (epiligrin) regulates tyrosine phosphorylation of a membrane-associated 80-kD protein. J Cell Biol 132: 727–740, 1996Google Scholar
  55. 55.
    Pyke C, Salu S, Ralfkiaer E, Rumer J, Danu K, Tiyggvason K: Laminin-5 is a marker of invading cancer cells in some human carcinomas and is coexpressed with the receptor for urokinase plasminogen activator in budding cancer cells in colon adenocarcinomas. Cancer Res 55: 4132–4139, 1995Google Scholar
  56. 56.
    Pyke C, Romer J, Kallunki P, Lund LR, Ralfkiaer E, Dano K, Tryggvason K: The gamma 2 chain of kalinin/laminin 5 is preferentially expressed in invading malignant cells in human cancers. Am J Pathol 145: 782–791, 1994Google Scholar

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • George E. Plopper
    • 1
  • Susan Z. Domanico
    • 1
  • Vincenzo Cirulli
    • 2
  • William B. Kiosses
    • 1
  • Vito Quaranta
    • 1
  1. 1.Department of Cell Biology/SBR12The Scripps Research InstituteLa JollaUSA
  2. 2.The Whittier Institute, Department of PediatricsUniversity of California San DiegoLa JollaUSA

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