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Cell adhesion molecules in the normal and cancerous mammary gland

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Loss of normal tissue morphology is one of the first changes seen in the development of solid malignant tumours, including breast cancers. Since cell adhesion molecules play a crucial role in maintaining normal tissue architecture, investigations into the molecular mechanisms involved in the morphological changes occurring in malignancy that focus on the expression and function of cell adhesion molecules in malignant progression are extremely relevant. This review discusses the cadherin and integrin families of adhesion molecules which have been shown to be extremely important in the cell-cell and cell-matrix interactions of epithelial cells. Immunohistochemical studies using tissue and tumour sections indicate that a reduction in levels of expression or function of both types of cell adhesion molecules is indeed observed in many breast cancers. A specific and crucial role for these molecules in the maintenance of normal morphological differentiation has been demonstratedin vitro, where the noninvasive differentiated phenotype correlates with the normal functioning of E-Cadherin and α2β1 integrin. Furtherin vitro evidence suggests that in mammary epithelial cells, oncogenes may be upstream regulators of both the expression and function of E-Cadherin, the α2β1 integrin, and other epithelial specific molecules important for maintaining epithelial differentiation. In this way they could manifest their effects on the tumorigeneic potential of epithelial cells.

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References

  1. O. W. Petersen, P. E. Hoyer, and B. van Deurs (1987). Frequency and distribution of estrogen receptor-positive cells in normal, nonlactating human breast tissue.Cancer Res. 47:5748–5751.

    PubMed  Google Scholar 

  2. J. Taylor-Papadimitriou and E. B. Lane (1987). Keratin expression in the mammary gland. In M. C. Neville and C. W. Daniel (eds.),The Mammary Gland, Plenum, New York, pp. 181–215.

    Google Scholar 

  3. B. E. Symington, Y. Takada, and W. G. Carter (1993). Interaction of integrins alpha 3 beta 1 and alpha 2 beta 1: potential role in keratinocyte intercellular adhesion.J. Cell Biol. 120:523–535.

    PubMed  Google Scholar 

  4. P. Sriramarao, P. Steffner, and K. R. Gehlsen (1993). Tiochemical evidence for a homophilic interaction of the alpha of the alpha 3 beta 1 integrin.J. Biol. Chem. 268:22036–22041.

    PubMed  Google Scholar 

  5. R. O. Hynes (1992). Integrins: versatility, modulation, and signaling in cell adhesion.Cell 69:11–25.

    PubMed  Google Scholar 

  6. F. Berdichevsky, D. Alford, B. D'Souza, and J. Taylor-Papadimitriou (1994). Branching morphogenesis of human mammary epithelial cells in collagen gels.J. Cell Sci. 107:3557–3568.

    PubMed  Google Scholar 

  7. R. Kemler (1993). From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion.Trends Genet. 9:317–321.

    PubMed  Google Scholar 

  8. C. L. Sommers (1996). The role of cadherin-mediated adhesion in breast cancer.J. Mam. Gland Biol. Neoplasia 1(2):219–229.

    Google Scholar 

  9. S. A. Rasbridge, C. E. Gillett, S. A. Sampson, F. S. Walsh, and R. R. Millis (1993). Epithelial (E-) and placental (P-) cadherin cell adhesion molecule expression in breast carcinoma.J. Pathol. 169:245–250.

    PubMed  Google Scholar 

  10. J. L. Jones, D. R. Critchley, and R. A. Walker (1992). Alteration of stromal protein and integrin expression in breast—a marker of premalignant change?J. Pathol. 167:399–406.

    PubMed  Google Scholar 

  11. M. M. Zutter, G. Mazoujian, and S. A. Santoro (1990). Decreased expression of integrin adhesive protein receptors in adenocarcinoma of the breast.Am. J. Pathol. 137:863–870.

    PubMed  Google Scholar 

  12. M. M. Zutter, H. R. Krigman, and S. A. Santoro (1993). Altered integrin expression in adenocarcinoma of the breast. Analysis byin situ hybridization.Am. J. Pathol. 142:1439–1448.

    PubMed  Google Scholar 

  13. M. Pignatelli, A. M. Hanby, and G. W. Stamp (1991). Low expression of beta 1, alpha 2 and alpha 3 subunits of VLA integrins in malignant mammary tumors.J. Pathol. 165:25–32.

    PubMed  Google Scholar 

  14. F. Berdichevsky, R. Wetzels, M. Shearer, S. Martignone, F. C. S. Ramaekers, and J. Taylor-Papadimitriou (1994). Integrin expression in relation to cell phenotype and malignant change in the human breast.Mol. Cell. Diff. 2:255–274.

    Google Scholar 

  15. M. Glukhova, V. Koteliansky, X. Sastre, and J. P. Thiery (1995). Adhesion systems in normal breast and in invasive breast carcinoma.Am. J. Pathol. 146:706–716.

    PubMed  Google Scholar 

  16. K. Friedrichs, P. Ruiz, F. Franke, I. Gille, H. J. Terpe, and B. A. Imhof (1995). High expression level of alpha 6 integrin in human breast carcinoma is correlated with reduced survival.Cancer Res. 55:901–906.

    PubMed  Google Scholar 

  17. J. Taylor-Papadimitriou (1992). Normal cell lineages and the phenotype of the breast cancer cell. In A. Goldhirsch (ed.),Endocrine Therapy of Breast Cancer V, Springer-Verlag, Berlin, Heidelberg New York, pp. 3–16.

    Google Scholar 

  18. A. J. D'Ardenne, P. I. Richman, M. A. Horton, A. E. Mcaulay, and S. Jordan (1991). Co-ordinate expression of the alpha-6 integrin laminin receptor sub-unit and laminin in breast cancer.J. Pathol. 165:213–220.

    PubMed  Google Scholar 

  19. C. Gamallo, J. Palacios, A. Suarez, A. Pizarro, P. Navarro, M. Quintanilla, and A. Cano (1993). Correlation of E-Cadherin expression with differentiation grade and histological type in breast carcinoma.Am. J. Pathol. 142:987–993.

    PubMed  Google Scholar 

  20. H. Oka, H. Shiozaki, K. Kobayashi, M. Inoue, H. Tahara, T. Kobayashi, Y. Takatsuka, N. Matsuyoshi, S. Hirano, M. Takeichi, and M. Takesada (1993). Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis.Cancer Res. 53:1696–1701.

    PubMed  Google Scholar 

  21. R. Moll, M. Mitze, U. H. Frixen, and W. Birchmeier (1993). Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas.Am. J. Pathol. 143:1731–1742.

    PubMed  Google Scholar 

  22. T. Takayama, H. Shiozaki, M. Inoue, S. Tamura, H. Oka, T. Kadowaki, Y. Takatsuka, A. Nagafuchi, S. Tsukita, and T. Mori (1994). Expression of E-Cadherin and α-catenin molecules in human breast cancer tissues and association with clinicophatological features.Int. J. Oncol. 5:775–780.

    Google Scholar 

  23. J. Palacios, N. Benito, A. Pizarro, A. Suarez, J. Espada, A. Cano, and C. Gamallo (1995). Anomalous expression of P-cadherin in breast carcinoma. Correlation with E-cadherin expression and pathological features.Am. J. Pathol. 146:605–612.

    Google Scholar 

  24. J. Bartek, J. Bartkova, N. Kyprianou, E. N. Lalani, Z. Staskova, M. Shearer, S. Chang, and J. Taylor-Papadimitriou (1991). Efficient immortalization of luminal epithelial cells from human mammary gland by introduction of simian virus 40 large tumor antigen with a recombinant retrovirus.Proc. Natl. Acad. Sci. U.S.A. 88:3520–3524.

    PubMed  Google Scholar 

  25. M. Shearer, J. Bartkova, J. Bartek, F. Berdichevsky, D. Barnes, R. Millis, and J. Taylor-Papadimitriou (1992). Studies of clonal cell lines developed from primary breast cancers indicate that the ability to undergo morphogenesisin vitro is lost early in malignancy.Int. J. Cancer 51:602–612.

    PubMed  Google Scholar 

  26. A. R. Howlett, N. Bailey, C. Damsky, O. W. Petersen, and M. J. Bissell (1995). Cellular growth and survival are mediated by β1 integrins in normal human breast epithelium but not in breast carcinoma.J. Cell Sci. 108:1945–1957.

    PubMed  Google Scholar 

  27. S. M. Frisch and H. Francis (1994). Disruption of epithelial cell-matrix interactions induces apoptosis.J. Cell Biol. 124:619–626.

    PubMed  Google Scholar 

  28. M. M. Zutter, S. A. Santoro, W. D. Staatz, and Y. L. Tsung (1995). Re-expression of the α2β1 integrin abrogates the malignant phenotype of breast carcinoma cells.Proc. Natl. Acad. Sci. U.S.A. 92:7411–7415.

    PubMed  Google Scholar 

  29. U. H. Frixen, J. Behrens, M. Sachs, G. Eberle, B. Voss, A. Warda, D. Lochner, and W. Birchmeier (1991). E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells.J. Cell Biol. 113:173–185.

    PubMed  Google Scholar 

  30. K. Vleminckx, L. J. Vakaet, M. Mareel, W. Fiers, and F. van Roy (1991). Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role.Cell 66:107–119.

    PubMed  Google Scholar 

  31. C. L. Sommers, E. W. Thompson, J. A. Torri, R. Kemler, E. P. Gelmann, and S. W. Byers (1991). Cell adhesion molecule uvomorulin expression in human breast cancer cell lines: relationship to morphology and invasive capacities.Cell Growth Diff. 2:365–372.

    PubMed  Google Scholar 

  32. C. L. Sommers, E. P. Gelmann, R. Kemler, P. Cowin, and S. W. Byers (1994). Alterations in beta-catenin phosphorylation and plakoglobin expression in human breast cancer cells.Cancer Res. 54:3544–3552.

    PubMed  Google Scholar 

  33. B. D'Souza, F. Berdichevsky, N. Kyprianou, and J. Taylor-Papadimitriou (1993). Collagen-induced morphogenesis and expression of the alpha 2-integrin subunit is inhibited in c-erbB2-transfected human mammary epithelial cells.Oncogene 8:1797–1806.

    PubMed  Google Scholar 

  34. P. J. Lu, Q. L. Lu, A. Rughetti, and J. Taylor-Papadimitriou (1995). bcl-2 overexpression inhibits cell death and promotes the morphogenesis, but not tumorigenesis of human mammary epithelial cells.J. Cell Biol. 129:1363–1378.

    PubMed  Google Scholar 

  35. M. S. Kinch, G. J. Clark, C. J. Der, and K. Burridge (1995). Tyrosine phosphorylation regulates the adhesions ofras-transformed breast epithelia.J. Cell Biol. 130:461–471.

    PubMed  Google Scholar 

  36. B. D'Souza and J. Taylor-Papadimitriou (1994). Overexpression of ERBB2 in human mammary epithelial cells signals inhibition of transcription of the E-cadherin gene.Proc. Natl. Acad. Sci. U.S.A. 91:7202–7206.

    PubMed  Google Scholar 

  37. S. Shibamoto, M. Hayakawa, K. Takeuchi, T. Hori, N. Oku, K. Miyazawa, N. Kitamura, M. Takeichi, and F. Ito (1994). Tyrosine phosphorylation of beta-catenin and plakoglobin enhanced by hepatocyte growth factor and epidermal growth factor in human carcinoma cells.Cell Adhes. Commun. 1:295–305.

    PubMed  Google Scholar 

  38. E. Reichmann, H. Schwarz, E. M. Deiner, I. Leitner, M. Eilers, J. Berger, M. Busslinger, and H. Beug (1992). Activation of an inducible c-FosER fusion protein causes loss of epithelial polarity and triggers epithelial-fibroblastoid cell conversion.Cell 71:1103–1116.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Epithelial Cell Biology Laboratory, Room 222, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, WC2A 3PX, London, UK

    Deborah Alford & Joyce Taylor-Papadimitriou

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  1. Deborah Alford
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  2. Joyce Taylor-Papadimitriou
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Correspondence to Joyce Taylor-Papadimitriou.

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Alford, D., Taylor-Papadimitriou, J. Cell adhesion molecules in the normal and cancerous mammary gland. J Mammary Gland Biol Neoplasia 1, 207–218 (1996). https://doi.org/10.1007/BF02013644

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