• Tracy L. Davis
  • Aaron J. Goldman
  • Anne E. Cress
Part of the Cancer Metastasis – Biology and Treatment book series (CMBT, volume 9)


An early step in epithelial cancer progression is the loss of cell adhesion structures and the persistence of selected sets of adhesion proteins. In this chapter, the data from immunohistochemical analysis of human tissue and published DNA microarray results from human tissue are discussed to illustrate the altered expression of cell adhesion structures in carcinomas. Further, the role of adhesion structures in cancer metastasis is discussed and the inherited alterations in adhesion molecules associated with increased risk for certain carcinomas is detailed. Finally, the potential utility of elements of the adhesion structures as surrogate and end point biomarkers is discussed.


Squamous Cell Carcinoma Focal Adhesion Kinase Basal Cell Carcinoma Bullous Pemphigoid Epidermolysis Bullosa 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Van den Bergh, F., Giudice, G.J. BP180 (type XVII collagen) and its role in cutaneousbiology and disease. Adv Dermatol, 2003; 19:37–71.PubMedGoogle Scholar
  2. 2.
    Sterk, L.M., Geuijen, C.A., Van den Bergh, J.G., Claessen, N., Weening, J.J., Sonnenberg, A. Association of the tetraspanin CD151 with the laminin-binding integrins alpha3beta1, alpha6beta1, alpha6beta4 and alpha7beta1 in cells in culture and in vivo. J Cell Sci2002.June 15:115(pt12):2615.Google Scholar
  3. 3.
    Koster, J., van Wilpe, S., Kuikman, I., Litjens, S.H., Sonnenberg, A. Role of binding of plectin to the integrin beta4 subunit in the assembly of hemidesmosomes. Mol Biol Cell, 2004 Mar; 15(3):1211–23. Epub 2003 Dec.Google Scholar
  4. 4.
    Hynes, R.O. Integrins: bidirectional, allosteric signaling machines. Cell. 2002 Sep 20;110(6):673–87.Google Scholar
  5. 5.
    Nievers, M.G., Kuikman I., Geerts, D., Leigh, I.M., Sonnenberg, A. Formation of hemidesmosome-like structures in the absence of ligand binding by the (alph) 6(beta)4 integrin requires binding of HD1/plectin to the cytoplasmic domain of the (beta)4 integrinsubunit. J Cell Sci. 2000 Mar; 113 (Pt 6):963–73.Google Scholar
  6. 6.
    Nagle, R.B., et al., Expression of hemidesmosomal and extracellular matrix proteins bynormal and malignant human prostate tissue. Am J Pathol, 1995. 146(6): p. 1498–507.PubMedGoogle Scholar
  7. 7.
    Cress, A.E., et al., The alpha 6 beta 1 and alpha 6 beta 4 integrins in human prostate cancer progression. Cancer Metastasis Rev, 1995. 14(3): p. 219–28.PubMedGoogle Scholar
  8. 8.
    Knox, J.D., et al., Differential expression of extracellular matrix molecules and the alpha 6-integrins in the normal and neoplastic prostate. Am J Pathol, 1994. 145(1): p. 167–74.PubMedGoogle Scholar
  9. 9.
    Nagle, R.B., et al., Adhesion molecules, extracellular matrix, and proteases in prostate carcinoma. J Cell Biochem Suppl, 1994. 19: p. 232–7.PubMedGoogle Scholar
  10. 10.
    Bonkhoff, H., Analytical molecular pathology of epithelial-stromal interactions in the normal and neoplastic prostate. Anal Quant Cytol Histol, 1998. 20(5): p. 437–42.PubMedGoogle Scholar
  11. 11.
    Allen, M.V., et al., Downregulation of the beta4 integrin subunit in prostatic carcinoma and prostatic intraepithelial neoplasia. Hum Pathol, 1998. 29(4): p. 311–8.PubMedGoogle Scholar
  12. 12.
    Bonkhoff, H., Stein, U. and Remberger, K. Differential expression of alpha 6 and alpha 2 very late antigen integrins in the normal, hyperplastic, and neoplastic prostate: simultaneous demonstration of cell surface receptors and their extracellular ligands. Hum Pathol, 1993. 24(3): p. 243–8.PubMedGoogle Scholar
  13. 13.
    Davis, T.L., et al., Unique expression pattern of the alpha6beta4 integrin and laminin-5 in human prostate carcinoma. Prostate, 2001. 46(3): p. 240–8.PubMedGoogle Scholar
  14. 14.
    Tagliabue, E., et al., Prognostic value of alpha 6 beta 4 integrin expression in breast carcinomas is affected by laminin production from tumor cells. Clin Cancer Res, 1998. 4(2): p. 407–10.PubMedGoogle Scholar
  15. 15.
    Jones, J.L., Critchley, D.R. and Walker, R.A. Alteration of stromal protein and integrin expression in breast–a marker of premalignant change? J Pathol, 1992. 167(4): p. 399–406.PubMedGoogle Scholar
  16. 16.
    Bahadoran, P. , et al., Altered expression of the hemidesmosome-anchoring filament complex proteins in basal cell carcinoma: possible role in the origin of peritumoral lacunae. Br J Dermatol, 1997. 136(1): p. 35–42.PubMedGoogle Scholar
  17. 17.
    Chopra, A., Maitra, B. and Korman, N.J. Decreased mRNA expression of several basement membrane components in basal cell carcinoma. J Invest Dermatol, 1998. 110(1): p. 52–6.PubMedGoogle Scholar
  18. 18.
    Dumas, V., et al., Expression of basement membrane antigens and matrix metalloproteinases 2 and 9 in cutaneous basal and squamous cell carcinomas. Anticancer Res, 1999. 19(4B): p. 2929–38.PubMedGoogle Scholar
  19. 19.
    Herold-Mende, C., et al., Metastatic growth of squamous cell carcinomas is correlated with upregulation and redistribution of hemidesmosomal components. Cell Tissue Res, 2001. 306(3): p. 399–408.PubMedGoogle Scholar
  20. 20.
    Tennenbaum, T., et al., Extracellular matrix receptors and mouse skin carcinogenesis: altered expression linked to appearance of early markers of tumor progression. Cancer Res, 1992. 52(10): p. 2966–76.PubMedGoogle Scholar
  21. 21.
    Witkowski, C.M., et al., Altered surface expression and increased turnover of the alpha6beta4 integrin in an undifferentiated carcinoma. Carcinogenesis, 2000. 21(2): p. 325–30.PubMedGoogle Scholar
  22. 22.
    Garzino-Demo, P. , et al., Altered expression of alpha 6 integrin subunit in oral squamous cell carcinoma and oral potentially malignant lesions. Oral Oncol, 1998. 34(3): p. 204–10.PubMedGoogle Scholar
  23. 23.
    Skubitz, A.P. , et al., Expression of alpha 6 and beta 4 integrins in serous ovarian carcinoma correlates with expression of the basement membrane protein laminin. Am J Pathol, 1996. 148(5): p. 1445–61.PubMedGoogle Scholar
  24. 24.
    Carlevato, M.T., et al., Differential integrin expression in thyroid and laryngeal carcinomas. Anticancer Res, 1996. 16(4C): p. 2379–84.PubMedGoogle Scholar
  25. 25.
    Pouliot, N., Nice, E.C., and Burgess, A.W. Laminin-10 mediates basal and EGF- stimulated motility of human colon carcinoma cells via alpha(3)beta(1) and alpha(6)beta(4) integrins. Exp Cell Res, 2001. 266(1): p. 1–10.PubMedGoogle Scholar
  26. 26.
    Lohi, J., et al., Basement membrane laminin-5 is deposited in colorectal adenomas and carcinomas and serves as a ligand for alpha3beta1 integrin. Apmis, 2000. 108(3): p. 161–72.PubMedGoogle Scholar
  27. 27.
    Fontao, L., et al., Polarized expression of HD1: relationship with the cytoskeleton in cultured human colonic carcinoma cells. Exp Cell Res, 1997. 231(2): p. 319–27.PubMedGoogle Scholar
  28. 28.
    Chao, C., et al., A function for the integrin alpha6beta4 in the invasive properties of colorectal carcinoma cells. Cancer Res, 1996. 56(20): p. 4811–9.PubMedGoogle Scholar
  29. 29.
    Van Waes, C., et al., The A9 antigen associated with aggressive human squamous carcinoma is structurally and functionally similar to the newly defined integrin alpha 6 beta 4. Cancer Res, 1991. 51(9): p. 2395–402.PubMedGoogle Scholar
  30. 30.
    Sordat, I., et al., Differential expression of laminin-5 subunits and integrin receptors in human colorectal neoplasia. J Pathol, 1998. 185(1): p. 44–52.PubMedGoogle Scholar
  31. 31.
    Stallmach, A., et al., Diminished expression of integrin adhesion molecules on human colonic epithelial cells during the benign to malign tumour transformation. Gut, 1992. 33(3): p. 342–6.PubMedGoogle Scholar
  32. 32.
    Geuijen, C.A. and Sonnenberg, A. Dynamics of the alpha6beta4 Integrin in Keratinocytes. Mol Biol Cell, 2002. 13(11): p. 3845–58.PubMedGoogle Scholar
  33. 33.
    Tsuruta, D., Hopkinson, S.B., and Jones, J.C. Hemidesmosome protein dynamics in live epithelial cells. Cell Motil Cytoskeleton, 2003. 54(2): p. 122–34.PubMedGoogle Scholar
  34. 34.
    Uematsu, J., et al., Demonstration of type II hemidesmosomes in a mammary gland epithelial cell line, BMGE-H. J Biochem (Tokyo), 1994. 115(3): p. 469–76.Google Scholar
  35. 35.
    Fontao, L., et al., Regulation of the type II hemidesmosomal plaque assembly in intestinal epithelial cells. Exp Cell Res, 1999. 250(2): p. 298–312.PubMedGoogle Scholar
  36. 36.
    Hieda, Y., et al., Identification of a new hemidesmosomal protein, HD1: a major, high molecular mass component of isolated hemidesmosomes. J Cell Biol, 1992. 116(6): p. 1497–506.PubMedGoogle Scholar
  37. 37.
    Posteraro, P., DeLuca, N., Meneguzzi, G., El Hachem, M., Angelo, C., Gobello, T., Tadini, G., Zambruno, G., Castiglia, D. Laminin-5 mutational analysis in an Italian cohort of patients with junctional epidermolysis bullosa. J Invest Dermatol, 2004 Oct;123(4):xii–xiii.Google Scholar
  38. 38.
    Rousselle, P., et al., Laminin 5 binds the NC-1 domain of type VII collagen. J Cell Biol, 1997. 138(3): p. 719–28.PubMedGoogle Scholar
  39. 39.
    Hao, J., et al., Differential expression of laminin 5 (alpha 3 beta 3 gamma 2) by human malignant and normal prostate. Am J Pathol, 1996. 149(4): p. 1341–9.PubMedGoogle Scholar
  40. 40.
    Hao, J., et al., Investigation into the mechanism of the loss of laminin 5 (alpha3beta3- gamma2) expression in prostate cancer. Am J Pathol, 2001. 158(3): p. 1129–35.PubMedGoogle Scholar
  41. 41.
    Ernst, T., et al., Decrease and gain of gene expression are equally discriminatory markers for prostate carcinoma: a gene expression analysis on total and microdissected prostate tissue. Am J Pathol, 2002. 160(6): p. 2169–80.PubMedGoogle Scholar
  42. 42.
    Maatta, M., et al., Comparative analysis of the distribution of laminin chains in the basement membranes in some malignant epithelial tumors: the alpha1 chain of laminin shows a selected expression pattern in human carcinomas. J Histochem Cytochem, 2001. 49(6): p. 711–26.PubMedGoogle Scholar
  43. 43.
    Daigo, Y., et al., Degenerate oligonucleotide primed-polymerase chain reaction-based array comparative genomic hybridization for extensive amplicon profiling of breast cancers : a new approach for the molecular analysis of paraffin-embedded cancer tissue. Am J Pathol, 2001. 158(5): p. 1623–31.PubMedGoogle Scholar
  44. 44.
    Aoki, S., et al., Prognostic significance of laminin-5 gamma2 chain expression in colorectal carcinoma: immunohistochemical analysis of 103 cases. Dis Colon Rectum, 2002. 45(11): p. 1520–7.PubMedGoogle Scholar
  45. 45.
    Li, K., et al., Cloning of partial cDNA for mouse 180-kDa bullous pemphigoid antigen (BPAG2), a highly conserved collagenous protein of the cutaneous basement membrane zone. J Invest Dermatol, 1992. 99(3): p. 258–63.PubMedGoogle Scholar
  46. 46.
    Hopkinson, S.B. and Jones, J.C. The N terminus of the transmembrane protein BP180 interacts with the N-terminal domain of BP230, thereby mediating keratin cytoskeleton anchorage to the cell surface at the site of the hemidesmosome. Mol Biol Cell, 2000. 11(1): p. 277–86.PubMedGoogle Scholar
  47. 47.
    Koster, J., et al., Analysis of the interactions between BP180, BP230, plectin and the integrin alpha6beta4 important for hemidesmosome assembly. J Cell Sci, 2003. 116(Pt 2): p. 387–399.PubMedGoogle Scholar
  48. 48.
    Hopkinson, S.B., Baker, S.E., and Jones, J.C. Molecular genetic studies of a human epidermal autoantigen (the 180-kD bullous pemphigoid antigen/BP180): identification of functionally important sequences within the BP180 molecule and evidence for an interaction between BP180 and alpha 6 integrin. J Cell Biol, 1995. 130(1): p. 117–25.PubMedGoogle Scholar
  49. 49.
    Hopkinson, S.B., et al., Interaction of BP180 (type XVII collagen) and alpha6 integrin is necessary for stabilization of hemidesmosome structure. J Invest Dermatol, 1998. 111(6): p. 1015–22.PubMedGoogle Scholar
  50. 50.
    Tanaka, M., et al., Characterization of bullous pemphigoid antibodies by use of recombi-nant bullous pemphigoid antigen proteins. J Invest Dermatol, 1991. 97(4): p. 725–8.PubMedGoogle Scholar
  51. 51.
    Ruhrberg, C. and Watt, F.M. The plakin family: versatile organizers of cytoskeletal architecture. Curr Opin Genet Dev, 1997. 7(3): p. 392–7.PubMedGoogle Scholar
  52. 52.
    Bergstraesser, L.M., et al., Expression of hemidesmosomes and component proteins is lost by invasive breast cancer cells. Am J Pathol, 1995. 147(6): p. 1823–39.PubMedGoogle Scholar
  53. 53.
    Zhu, X.J., Niimi, Y., and Bystryn, J.C. Identification of a 160-kD molecule as a component of the basement membrane zone and as a minor bullous pemphigoid antigen. J Invest Dermatol, 1990. 94(6): p. 817–21.PubMedGoogle Scholar
  54. 54.
    Fairley, J.A., et al., Expression pattern of the bullous pemphigoid-180 antigen in normal and neoplastic epithelia. Br J Dermatol, 1995. 133(3): p. 385–91.PubMedGoogle Scholar
  55. 55.
    Yamada, T., et al., Aberrant expression of a hemidesmosomal protein, bullous pemphigoid antigen 2, in human squamous cell carcinoma. Lab Invest, 1996. 75(4): p. 589–600.PubMedGoogle Scholar
  56. 56.
    Schaapveld, R.Q., et al., Hemidesmosome formation is initiated by the beta4 integrin subunit, requires complex formation of beta4 and HD1/plectin, and involves a direct interaction between beta4 and the bullous pemphigoid antigen 180. J Cell Biol, 1998. 142(1): p. 271–84.PubMedGoogle Scholar
  57. 57.
    Burgeson, R.E., Type VII collagen, anchoring fibrils, and epidermolysis bullosa. J Invest Dermatol, 1993. 101(3): p. 252–5.PubMedGoogle Scholar
  58. 58.
    Keene, D.R., et al., Type VII collagen forms an extended network of anchoring fibrils. J Cell Biol, 1987. 104(3): p. 611–21.PubMedGoogle Scholar
  59. 59.
    Liebert, M., et al., Loss of co-localization of alpha 6 beta 4 integrin and collagen VII in bladder cancer. Am J Pathol, 1994. 144(4): p. 787–95.PubMedGoogle Scholar
  60. 60.
    Fuchs, E., Keratins and the skin. Annu Rev Cell Dev Biol, 1995. 11: p. 123–53.PubMedGoogle Scholar
  61. 61.
    Irvine, A.D. and McLean, W.H. Human keratin diseases: the increasing spectrum of disease and subtlety of the phenotype-genotype correlation. Br J Dermatol, 1999. 140(5): p. 815–28.PubMedGoogle Scholar
  62. 62.
    Quinlan, R., Hutchison, C., and Lane, B. Intermediate filament proteins. Protein Profile, 1994. 1(8): p. 779–911.PubMedGoogle Scholar
  63. 63.
    Goldstein, N.S., Immunophenotypic characterization of 225 prostate adenocarcinomas with intermediate or high Gleason scores. Am J Clin Pathol, 2002. 117(3): p. 471–7.PubMedGoogle Scholar
  64. 64.
    Yang, Y., et al., Differential expression of cytokeratin mRNA and protein in normal prostate, prostatic intraepithelial neoplasia, and invasive carcinoma. Am J Pathol, 1997. 150(2): p. 693–704.PubMedGoogle Scholar
  65. 65.
    Abrahams, N.A., Ormsby, A.H. and Brainard, J. Validation of cytokeratin 5/6 as aneffective substitute for keratin 903 in the differentiation of benign from malignant glands in prostate needle biopsies. Histopathology, 2002. 41(1): p. 35–41.PubMedGoogle Scholar
  66. 66.
    Sherwood, E.R., et al., Differential expression of specific cytokeratin polypeptides in the basal and luminal epithelia of the human prostate. Prostate, 1991. 18(4): p. 303–14.PubMedGoogle Scholar
  67. 67.
    Wang, W., et al., Single cell behavior in metastatic primary mammary tumors correlatedwith gene expression patterns revealed by molecular profiling. Cancer Res, 2002. 62(21):p. 6278–88.PubMedGoogle Scholar
  68. 68.
    Tsubura, A., et al., Keratin expression in the normal breast and in breast carcinoma. Histopathology, 1991. 18(6): p. 517–22.PubMedGoogle Scholar
  69. 69.
    Tot, T., The cytokeratin profile of medullary carcinoma of the breast. Histopathology, 2000. 37(2): p. 175–81.PubMedGoogle Scholar
  70. 70.
    Schirren, C.G., et al., Trichoblastoma and basal cell carcinoma are neoplasms with follicular differentiation sharing the same profile of cytokeratin intermediate filaments. Am J Dermatopathol, 1997. 19(4): p. 341–50.PubMedGoogle Scholar
  71. 71.
    Shinohara, M., et al., Immunohistochemical study of desmosomes in oral squamous cellcarcinoma: correlation with cytokeratin and E-cadherin staining, and with tumour behaviour. J Pathol, 1998. 184(4): p. 369–81.PubMedGoogle Scholar
  72. 72.
    Pittella, F., et al., Perinuclear and cytoplasmic distribution of desmoglein in esophageal squamous cell carcinomas. Pathol Res Pract, 2001. 197(2): p. 85–91.PubMedGoogle Scholar
  73. 73.
    Kallakury, B.V., et al., Decreased expression of catenins (alpha and beta), p120 CTN, and E-cadherin cell adhesion proteins and E-cadherin gene promoter methylation in prostatic adenocarcinomas. Cancer, 2001. 92(11): p. 2786–95.PubMedGoogle Scholar
  74. 74.
    Chesire, D.R., et al., Detection and analysis of beta-catenin mutations in prostate cancer. Prostate, 2000. 45(4): p. 323–34.PubMedGoogle Scholar
  75. 75.
    Davies, E.L., et al., The immunohistochemical expression of desmoplakin and its role in vivo in the progression and metastasis of breast cancer. Eur J Cancer, 1999. 35(6): p. 902–7.PubMedGoogle Scholar
  76. 76.
    Sommers, C.L., et al., Alterations in beta-catenin phosphorylation and plakoglobin expression in human breast cancer cells. Cancer Res, 1994. 54(13): p. 3544–52.PubMedGoogle Scholar
  77. 77.
    Hoover, K.B., Liao, S.Y., and Bryant, P.J. Loss of the tight junction MAGUK ZO-1 in breast cancer: relationship to glandular differentiation and loss of heterozygosity. Am J Pathol, 1998. 153(6): p. 1767–73.PubMedGoogle Scholar
  78. 78.
    Yoshiura, K., et al., Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc Natl Acad Sci USA, 1995. 92(16): p. 7416–9.PubMedGoogle Scholar
  79. 79.
    Tamura, G., et al., E-Cadherin gene promoter hypermethylation in primary human gastriccarcinomas. J Natl Cancer Inst, 2000. 92(7): p. 569–73.PubMedGoogle Scholar
  80. 80.
    Corn, P. G., et al., Frequent hypermethylation of the 5’ CpG island of E-cadherin in esophageal adenocarcinoma. Clin Cancer Res, 2001. 7(9): p. 2765–9.PubMedGoogle Scholar
  81. 81.
    Azarschab, P. , et al., Epigenetic control of E-cadherin (CDH1) by CpG methylation in metastasising laryngeal cancer. Oncol Rep, 2003. 10(2): p. 501–3.PubMedGoogle Scholar
  82. 82.
    Droufakou, S., et al., Multiple ways of silencing E-cadherin gene expression in lobular carcinoma of the breast. Int J Cancer, 2001. 92(3): p. 404–8.PubMedGoogle Scholar
  83. 83.
    Hazan, R.B., et al., Cadherin switch in tumor progression. Ann N Y Acad Sci, 2004. 1014: p. 155–63.PubMedGoogle Scholar
  84. 84.
    Rubin, M.A., et al., E-cadherin expression in prostate cancer: a broad survey using high-density tissue microarray technology. Hum Pathol, 2001. 32(7): p. 690–7.PubMedGoogle Scholar
  85. 85.
    Aho, S., et al., Specific sequences in p120ctn determine subcellular distribution of its multiple isoforms involved in cellular adhesion of normal and malignant epithelial cells. J Cell Sci, 2002. 115(Pt 7): p. 1391–402.PubMedGoogle Scholar
  86. 86.
    Kallakury, B.V., Sheehan, C.E. and Ross, J.S. Co-downregulation of cell adhesion proteins alpha- and beta-catenins, p120CTN, E-cadherin, and CD44 in prostatic adenocarcinomas. Hum Pathol, 2001. 32(8): p. 849–55.PubMedGoogle Scholar
  87. 87.
    Arenas, M.I., et al., E-, N- and P-cadherin, and alpha-, beta- and gamma-catenin protein expression in normal, hyperplastic and carcinomatous human prostate. Histochem J, 2000. 32(11): p. 659–67.PubMedGoogle Scholar
  88. 88.
    Moll, R., et al., Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol, 1993. 143(6): p. 1731–42.PubMedGoogle Scholar
  89. 89.
    Rimm, D.L., Sinard, J.H., and Morrow, J.S. Reduced alpha-catenin and E-cadherin expression in breast cancer. Lab Invest, 1995. 72(5): p. 506–12.PubMedGoogle Scholar
  90. 90.
    Dillon, D.A., et al., The expression of p120ctn protein in breast cancer is independent of alpha- and beta-catenin and E-cadherin. Am J Pathol, 1998. 152(1): p. 75–82.PubMedGoogle Scholar
  91. 91.
    Glukhova, M., et al., Adhesion systems in normal breast and in invasive breast carcinoma. Am J Pathol, 1995. 146(3): p. 706–16.PubMedGoogle Scholar
  92. 92.
    Pizarro, A., E-cadherin expression is frequently reduced in infiltrative basal cell carcinoma. J Dermatol, 2000. 27(12): p. 804–5.PubMedGoogle Scholar
  93. 93.
    Kooy, A.J., et al., Expression of E-cadherin, alpha- & beta-catenin, and CD44V6 and the subcellular localization of E-cadherin and CD44V6 in normal epidermis and basal cell carcinoma. Hum Pathol, 1999. 30(11): p. 1328–35.PubMedGoogle Scholar
  94. 94.
    Yamazaki, F., et al., Immunohistochemical detection for nuclear beta-catenin in sporadic basal cell carcinoma. Br J Dermatol, 2001. 145(5): p. 771–7.PubMedGoogle Scholar
  95. 95.
    Boonchai, W., et al., Expression of beta-catenin, a key mediator of the WNT signaling pathway, in basal cell carcinoma. Arch Dermatol, 2000. 136(7): p. 937–8.PubMedGoogle Scholar
  96. 96.
    Schuhmacher, C., et al., Loss of immunohistochemical E-cadherin expression in colon cancer is not due to structural gene alterations. Virchows Arch, 1999. 434(6): p. 489–95.PubMedGoogle Scholar
  97. 97.
    Hiscox, S. and Jiang, W.G. Expression of E-cadherin, alpha, beta and gamma-catenin in human colorectal cancer. Anticancer Res, 1997. 17(2B): p. 1349–54.PubMedGoogle Scholar
  98. 98.
    Raftopoulos, I., et al., Level of alpha-catenin expression in colorectal cancer correlates with invasiveness, metastatic potential, and survival. J Surg Oncol, 1998. 68(2): p. 92–9.PubMedGoogle Scholar
  99. 99.
    Sellin, J.H., et al., Increased beta-catenin expression and nuclear translocation accompany cellular hyperproliferation in vivo. Cancer Res, 2001. 61(7): p. 2899–906.PubMedGoogle Scholar
  100. 100.
    Takemasa, I., et al., Construction of preferential cDNA microarray specialized for human colorectal carcinoma: molecular sketch of colorectal cancer. Biochem Biophys Res Commun, 2001. 285(5): p. 1244–9.PubMedGoogle Scholar
  101. 101.
    Schmelz, M., et al., PEAZ-1: a new human prostate neoplastic epithelial cell line. Prostate, 2001. 48(2): p. 79–92.PubMedGoogle Scholar
  102. 102.
    Aberle, H., et al., The human plakoglobin gene localizes on chromosome 17q21 and is subjected to loss of heterozygosity in breast and ovarian cancers. Proc Natl Acad Sci USA, 1995. 92(14): p. 6384–8.PubMedGoogle Scholar
  103. 103.
    Klus, G.T., et al., Down-regulation of the desmosomal cadherin desmocollin 3 in human breast cancer. Int J Oncol, 2001. 19(1): p. 169–74.PubMedGoogle Scholar
  104. 104.
    Dervan, P.A., et al., Desmosomal plaque proteins are preserved in all grades of breast cancer. An immunohistochemical study utilizing monoclonal antibodies to desmoplakin. Am J Surg Pathol, 1988. 12(11): p. 855–60.PubMedGoogle Scholar
  105. 105.
    Tada, H., et al., Expression of desmoglein I and plakoglobin in skin carcinomas. J Cutan Pathol, 2000. 27(1): p. 24–9.PubMedGoogle Scholar
  106. 106.
    Lifschitz-Mercer, B., et al., Nuclear Localization of beta-Catenin and Plakoglobin in Primary and Metastatic Human Colonic Carcinomas, Colonic Adenomas, and Normal Colon. Int J Surg Pathol, 2001. 9(4): p. 273–9.PubMedGoogle Scholar
  107. 107.
    Rovin, J.D., et al., Expression of focal adhesion kinase in normal and pathologic human prostate tissues. Prostate, 2002. 53(2): p. 124–32.PubMedGoogle Scholar
  108. 108.
    Weiner, T.M., et al., Expression of focal adhesion kinase gene and invasive cancer. Lancet, 1993. 342(8878): p. 1024–5.PubMedGoogle Scholar
  109. 109.
    Cance, W.G., et al., Immunohistochemical analyses of focal adhesion kinase expression in benign and malignant human breast and colon tissues: correlation with preinvasive and invasive phenotypes. Clin Cancer Res, 2000. 6(6): p. 2417–23.PubMedGoogle Scholar
  110. 110.
    Lifschitz-Mercer, B., et al., Expression of the adherens junction protein vinculin in human basal and squamous cell tumors: relationship to invasiveness and metastatic potential. Hum Pathol, 1997. 28(11): p. 1230–6.PubMedGoogle Scholar
  111. 111.
    Porter, R.M., et al., Monoclonal antibodies to cytoskeletal proteins: an immunohistochemical investigation of human colon cancer. J Pathol, 1993. 170(4): p. 435–40.PubMedGoogle Scholar
  112. 112.
    Owens, L.V., et al., Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors. Cancer Res, 1995. 55(13): p. 2752–5.PubMedGoogle Scholar
  113. 113.
    Chlenski, A., et al., Organization and expression of the human zo-2 gene (tjp-2) in normal and neoplastic tissues. Biochem Biophys Acta, 2000. 1493(3): p. 319–24.PubMedGoogle Scholar
  114. 114.
    Gendreau, K.M. and Whalen, G.F. What can we learn from the phenomenon of preferential lymph node metastasis in carcinoma? J Surg Oncol, 1999. 70(3): p. 199–204.PubMedGoogle Scholar
  115. 115.
    Draffin, J.E., et al., CD44 potentiates the adherence of metastatic prostate and breast cancer cells to bone marrow endothelial cells. Cancer Res, 2004. 64(16): p. 5702–11.PubMedGoogle Scholar
  116. 116.
    Hill, A., et al., The emerging role of CD44 in regulating skeletal micrometastasis. Cancer Lett, 2005.Google Scholar
  117. 117.
    Lopez, J.I., et al., CD44 attenuates metastatic invasion during breast cancer progression. Cancer Res, 2005. 65(15): p. 6755–63.PubMedGoogle Scholar
  118. 118.
    Gong, Y., et al., Expression of cell adhesion molecules, CD44s and E-cadherin, and microvessel density in invasive micropapillary carcinoma of the breast. Histopathology, 2005. 46(1): p. 24–30.PubMedGoogle Scholar
  119. 119.
    O'Hanlon, D.M., et al., Soluble adhesion molecules (E-selectin, ICAM-1 and VCAM-1) in breast carcinoma. Eur J Cancer, 2002. 38(17): p. 2252–7.PubMedGoogle Scholar
  120. 120.
    Hashida, H., et al., Integrin alpha3 expression as a prognostic factor in colon cancer: association with MRP-1/CD9 and KAI1/CD82. Int J Cancer, 2002. 97(4): p. 518–25.PubMedGoogle Scholar
  121. 121.
    Nanashima, A., et al., Expression of adhesion molecules in hepatic metastases of colorectal carcinoma: relationship to primary tumours and prognosis after hepatic resection. J Gastroenterol Hepatol, 1999. 14(10): p. 1004–9.PubMedGoogle Scholar
  122. 122.
    Wu, Z.Y., et al., Expression of E-cadherin in gastric carcinoma and its correlation with lymph node micrometastasis. World J Gastroenterol, 2005. 11(20): p. 3139–43.PubMedGoogle Scholar
  123. 123.
    Bosch, F.X., et al., E-cadherin is a selective and strongly dominant prognostic factor in squamous cell carcinoma: a comparison of E-cadherin with desmosomal components. Int J Cancer, 2005. 114(5): p. 779–90.PubMedGoogle Scholar
  124. 124.
    Takayama, N., et al., Relationship between the expression of adhesion molecules in primary esophageal squamous cell carcinoma and metastatic lymph nodes. Anticancer Res, 2003. 23(6a): p. 4435–42.PubMedGoogle Scholar
  125. 125.
    Lear, J.T. and Smith, A.G. Basal cell carcinoma. Postgrad Med J, 1997. 73(863): p. 538–42.PubMedGoogle Scholar
  126. 126.
    Fine, J., et al., Epidermolysis bullosa: clinical, epidemiologic, and laboratory advances and the findings of the national epidermolysis bullosa registry. 1999, Baltimore: Johns Hopkins University Press.Google Scholar
  127. 127.
    Yamauchi, Y., Takahashi, K. and Shiotsu, H. Osteogenic sarcoma of the tibia in a patient with epidermolysis bullosa dystrophica. Clin Orthop, 1988(228): p. 273–7.Google Scholar
  128. 128.
    Martinez, L., Goodman, P. and Crow, W.N. Squamous cell carcinoma of the maxillary sinus and palate in epidermolysis bullosa: CT demonstration. J Comput Assist Tomogr, 1992. 16(2): p. 317–9.PubMedGoogle Scholar
  129. 129.
    Horn, H.M. and Tidman, M.J. The clinical spectrum of dystrophic epidermolysis bullosa. Br J Dermatol, 2002. 146(2): p. 267–74.PubMedGoogle Scholar
  130. 130.
    Lyons, J.A., et al., Successful Breast Conservation in a Patient with Epidermolysis Bullosa Simplex. Breast J, 1999. 5(6): p. 404–406.PubMedGoogle Scholar
  131. 131.
    Etienne, A., et al., [Epidermolysis bullosa acquisita and metastatic cancer of the uterine cervix]. Ann Dermatol Venereol, 1998. 125(5): p. 321–3.PubMedGoogle Scholar
  132. 132.
    Christiano, A.M., et al., Mutation-based prenatal diagnosis of Herlitz junctional pidermolysis bullosa. Prenat Diagn, 1997. 17(4): p. 343–54.PubMedGoogle Scholar
  133. 133.
    Hilal, L., et al., A homozygous insertion-deletion in the type VII collagen gene (COL7A1) in Hallopeau-Siemens dystrophic epidermolysis bullosa. Nat Genet, 1993. 5(3): p. 287–93.PubMedGoogle Scholar
  134. 134.
    Mellerio, J.E., et al., A recurrent glycine substitution mutation, G2043R, in the type VII collagen gene (COL7A1) in dominant dystrophic epidermolysis bullosa. Br J Dermatol, 1998. 139(4): p. 730–7.PubMedGoogle Scholar
  135. 135.
    Mallipeddi, R., Epidermolysis bullosa and cancer. Clin Exp Dermatol, 2002. 27(8): p. 616–23.PubMedGoogle Scholar
  136. 136.
    McGrath, J.A., et al., A homozygous nonsense mutation in the alpha 3 chain gene of laminin 5 (LAMA3) in Herlitz junctional epidermolysis bullosa: prenatal exclusion in a fetus at risk. Genomics, 1995. 29(1): p. 282–4.PubMedGoogle Scholar
  137. 137.
    Vidal, F., et al., Cloning of the laminin alpha 3 chain gene (LAMA3) and identification of a homozygous deletion in a patient with Herlitz junctional epidermolysis bullosa. Genomics, 1995. 30(2): p. 273–80.PubMedGoogle Scholar
  138. 138.
    Plkkinen, L., et al., Cloning of the beta 3 chain gene (LAMB3) of human laminin 5, a candidate gene in junctional epidermolysis bullosa. Genomics, 1995. 25(1): p. 192–8.139.Google Scholar
  139. 139.
    Pulkkinen, L. and J. Uitto, Mutation analysis and molecular genetics of epidermolysis bullosa. Matrix Biol, 1999. 18(1): p. 29–42.PubMedGoogle Scholar
  140. 140.
    Kivirikko, S., et al., Mutational hotspots in the LAMB3 gene in the lethal (Herlitz) type of junctional epidermolysis bullosa. Hum Mol Genet, 1996. 5(2): p. 231–7.PubMedGoogle Scholar
  141. 141.
    Pulkkinen, L., et al., Predominance of the recurrent mutation R635X in the LAMB3 gene in European patients with Herlitz junctional epidermolysis bullosa has implications for mutation detection strategy. J Invest Dermatol, 1997. 109(2): p. 232–7.PubMedGoogle Scholar
  142. 142.
    Pulkkinen, L., et al., Mutations in the gamma 2 chain gene (LAMC2) of kalinin/laminin 5 in the junctional forms of epidermolysis bullosa. Nat Genet, 1994. 6(3): p. 293–7.PubMedGoogle Scholar
  143. 143.
    Baudoin, C., et al., A novel homozygous nonsense mutation in the LAMC2 gene in patients with the Herlitz junctional epidermolysis bullosa. Hum Mol Genet, 1994. 3(10): p. 1909–10.PubMedGoogle Scholar
  144. 144.
    Aberdam, D., et al., Herlitz's junctional epidermolysis bullosa is linked to mutations in the gene (LAMC2) for the gamma 2 subunit of nicein/kalinin (LAMININ-5). Nat Genet, 1994. 6(3): p. 299–304.PubMedGoogle Scholar
  145. 145.
    McGrath, J.A., et al., Mutations in the 180-kD bullous pemphigoid antigen (BPAG2), a hemidesmosomal transmembrane collagen (COL17A1), in generalized atrophic benign epidermolysis bullosa. Nat Genet, 1995. 11(1): p. 83–6.PubMedGoogle Scholar
  146. 146.
    Pulkkinen, L., et al., Homozygous alpha6 integrin mutation in junctional epidermolysis bullosa with congenital duodenal atresia. Hum Mol Genet, 1997. 6(5): p. 669–74.PubMedGoogle Scholar
  147. 147.
    Ruzzi, L., et al., A homozygous mutation in the integrin alpha6 gene in junctional epidermolysis bullosa with pyloric atresia. J Clin Invest, 1997. 99(12): p. 2826–31.PubMedGoogle Scholar
  148. 148.
    Vidal, F., et al., Integrin beta 4 mutations associated with junctional epidermolysis bullosa with pyloric atresia. Nat Genet, 1995. 10(2): p. 229–34.PubMedGoogle Scholar
  149. 149.
    Koster, J., et al., Two different mutations in the cytoplasmic domain of the integrin beta 4 subunit in nonlethal forms of epidermolysis bullosa prevent interaction of beta 4 with plectin. J Invest Dermatol, 2001. 117(6): p. 1405–11.PubMedGoogle Scholar
  150. 150.
    Smith, F.J., et al., Plectin deficiency results in muscular dystrophy with epidermolysis bullosa. Nat Genet, 1996. 13(4): p. 450–7.PubMedGoogle Scholar
  151. 151.
    McLean, W.H., et al., Loss of plectin causes epidermolysis bullosa with muscular dystrophy: cDNA cloning and genomic organization. Genes Dev, 1996. 10(14): p. 1724–35.PubMedGoogle Scholar
  152. 152.
    Pulkkinen, L., et al., Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy. Hum Mol Genet, 1996. 5(10): p. 1539–46.PubMedGoogle Scholar
  153. 153.
    Chavanas, S., et al., A homozygous nonsense mutation in the PLEC1 gene in patients with epidermolysis bullosa simplex with muscular dystrophy. J Clin Invest, 1996. 98(10): p. 2196–200.PubMedGoogle Scholar
  154. 154.
    Weber, F., et al., Squamous cell carcinoma in junctional and dystrophic epidermolysis bullosa. Acta Derm Venereol, 2001. 81(3): p. 189–92.PubMedGoogle Scholar
  155. 155.
    Swensson, O. and Christophers, E. Generalized atrophic benign epidermolysis bullosa in 2 siblings complicated by multiple squamous cell carcinomas. Arch Dermatol, 1998. 134(2): p. 199–203.PubMedGoogle Scholar
  156. 156.
    Monk, B.E. and Pembroke, A.C. Epidermolysis bullosa with squamous cell carcinoma. Clin Exp Dermatol, 1987. 12(5): p. 373–4.PubMedGoogle Scholar
  157. 157.
    Mallipeddi, R., et al., Increased risk of squamous cell carcinoma in junctional epidermolysis bullosa. J Eur Acad Dermatol Venereol, 2004. 18(5): p. 521–6.PubMedGoogle Scholar
  158. 158.
    Lane, E.B., et al., A mutation in the conserved helix termination peptide of keratin 5 in hereditary skin blistering. Nature, 1992. 356(6366): p. 244–6.PubMedGoogle Scholar
  159. 159.
    Bonifas, J.M., Rothman, A.L. and Epstein, E.H. Jr., Epidermolysis bullosa simplex: evidence in two families for keratin gene abnormalities. Science, 1991. 254(5035): p. 1202–5.PubMedGoogle Scholar
  160. 160.
    Coulombe, P.A., et al., Point mutations in human keratin 14 genes of epidermolysis bullosa simplex patients: genetic and functional analyses. Cell, 1991. 66(6): p. 1301–11.PubMedGoogle Scholar
  161. 161.
    Ehrlich, P. , et al., A common keratin 5 gene mutation in epidermolysis bullosa simplex- Weber-Cockayne. J Invest Dermatol, 1995. 104(5): p. 877–9.PubMedGoogle Scholar
  162. 162.
    Sasaki, Y., et al., A recurrent keratin 14 mutation in Dowling-Meara epidermolysis bullosa simplex. Br J Dermatol, 1999. 141(4): p. 747–8.PubMedGoogle Scholar
  163. 163.
    Ma, L., et al., A ‘hot-spot’ mutation alters the mechanical properties of keratin filament networks. Nat Cell Biol, 2001. 3(5): p. 503–6.PubMedGoogle Scholar
  164. 164.
    Shemanko, C.S., et al., Laryngeal involvement in the Dowling-Meara variant of epidermolysis bullosa simplex with keratin mutations of severely disruptive potential. Br J Dermatol, 2000. 142(2): p. 315–20.PubMedGoogle Scholar
  165. 165.
    Bernerd, F., et al., Clues to epidermal cancer proneness revealed by reconstruction of DNA repair-deficient xeroderma pigmentosum skin in vitro. Proc Natl Acad Sci USA, 2001. 98(14): p. 7817–22.PubMedGoogle Scholar
  166. 166.
    Morykwas, M.J., et al., Growth and adherence of xeroderma pigmentosum keratinocytes in vitro. Ann Plast Surg, 1990. 24(4): p. 342–5.PubMedGoogle Scholar

Copyright information

© Springer 2006

Authors and Affiliations

  • Tracy L. Davis
    • 1
  • Aaron J. Goldman
    • 2
  • Anne E. Cress
    • 2
  1. 1.Department of PathologyMassachusetts General HospitalBostonUSA
  2. 2.Department of Molecular and Cellular BiologyUniversity of ArizonaTucsonUSA

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