Virchows Archiv

, Volume 451, Issue 5, pp 959–966

Altered expression of desmocollin 3, desmoglein 3, and β-catenin in oral squamous cell carcinoma: correlation with lymph node metastasis and cell proliferation

  • Lihong Wang
  • Tingjiao Liu
  • Yao Wang
  • Lei Cao
  • Mai Nishioka
  • Rodelio L. Aguirre
  • Ayataka Ishikawa
  • Li Geng
  • Norihiko Okada
Original Article

Abstract

Desmocollin 3 (Dsc3) and desmoglein 3 (Dsg3) are both transmembrane glycoproteins that belong to the cadherin family of calcium-dependent cell adhesion molecules. β-Catenin is a member of the cadherin–catenin complex that mediates homotypic cell–cell adhesion and is also an important molecule in the wnt signaling pathway. In this study, we examined the simultaneous expression level of Dsc3, Dsg3, and β-catenin in oral squamous cell carcinomas (OSCCs) and normal oral epithelia using immunohistochemistry. There was a significant correlation (p < 0.05) among the following variables in OSCCs: reduced or loss of expression of Dsc3, Dsg3, and β-catenin compared to normal oral epithelium, reduced or loss of expression of Dsc3 and histological grade (moderately or poorly differentiated), and reduced or loss of expression of β-catenin and lymph node metastasis. Furthermore, a positive correlation was found between reduced or loss of β-catenin staining and reduced or loss of Dsc3 staining in lymph node metastatic cancer tissue (r = 0.734, p < 0.05). These results suggest an abnormal expression of Dsc3, Dsg3, and β-catenin induced in the progression of oral carcinomas and that the Dsc3 expression level might be related to the regulation of β-catenin in lymph node metastasis and cell proliferation in OSCCs.

Keywords

Oral squamous cell carcinoma Desmosomal cadherins β-Catenin Lymph node metastasis Cell proliferation 

References

  1. 1.
    Alazawi WO, Morris LS, Stanley MA, Garrod DR, Coleman DR (2003) Altered expression of desmosomal components in high-grade squamous intraepithelial lesions of the cervix. Virchows Arch 443:51–56PubMedCrossRefGoogle Scholar
  2. 2.
    Barth AI, Nathke IS, Nelson WJ (1997) Cadherins, catenins and APC protein: interplay between cytoskeletal complexes and signaling pathways. Curr Opin Cell Biol 9:683–690PubMedCrossRefGoogle Scholar
  3. 3.
    Brasanac D, Boricic I, Todorovic V, Tomanovic N, Radojevic S (2005) Cyclin A and beta-catenin expression in actinic keratosis, Bowen’s disease and invasive squamous cell carcinoma of the skin. Br J Dermatol 153:1166–1175PubMedCrossRefGoogle Scholar
  4. 4.
    Chen X, Bonne S, Hatzfeld M, van Roy F, Green KJ (2002) Protein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and beta-catenin signaling. J Biol Chem 277:10512–10522PubMedCrossRefGoogle Scholar
  5. 5.
    Chidgey M (2002) Desmosomes and disease: an update. Histol Histopathol 17:1179–1192PubMedGoogle Scholar
  6. 6.
    Conacci-Sorrell M, Zhurinsky J, Ze’ev B (2002) The cadherin–catenin adhesion system in signalling and cancer. J Clin Invest 109:987–991PubMedCrossRefGoogle Scholar
  7. 7.
    Cui J, Zhou XD, Liu YK, Tang ZY, Zile MH (2001) Abnormal beta-catenin gene expression with invasiveness of primary hepatocellular carcinoma in China. World J Gastroenterol 7:542–546PubMedGoogle Scholar
  8. 8.
    Damjanov I, Fan F (2007) Tumors of the mouth, pharynx, nose, and paranasal sinuses. In: Damjanov I, Fan F (eds) Cancer grading manual. Springer, New York, pp 6–12Google Scholar
  9. 9.
    Depondt J, Shabana AH, Florescu-Zorila S, Gehanno P, Forest N (1999) Down-regulation of desmosomal molecules in oral and pharyngeal squamous cell carcinomas as a marker for tumour growth and distant metastasis. Eur J Oral Sci 107:183–193PubMedCrossRefGoogle Scholar
  10. 10.
    Garrod DR (1995) Desmosomes and cancer. Cancer Surv 24:97–111PubMedGoogle Scholar
  11. 11.
    Garrod DR, Merritt AJ, Nie Z (2002) Desmosomal cadherins. Curr Opin Cell Biol 14:537–545PubMedCrossRefGoogle Scholar
  12. 12.
    Getsios S, Huen AC, Green KJ (2004) Working out the strength and flexigility of desmosomes. Nat Rev Mol Cell Biol 5:271–281PubMedCrossRefGoogle Scholar
  13. 13.
    Hanakawa Y, Amagai M, Shirakata Y, Sayama K, Hashimoto K (2000) Different effects of dominant negative mutants of desmocollin and desmoglein on the cell–cell adhesion of keratinocytes. J Cell Sci 113:1803–1811PubMedGoogle Scholar
  14. 14.
    Hardman MJ, Liu K, Avilion AA, Merritt A, Brennan K, Garrod DR, Byrne C (2005) Desmosomal cadherin misexpression alters beta-catenin stability and epidermal differentiation. Mol Cell Biol 25:969–978PubMedCrossRefGoogle Scholar
  15. 15.
    Hiraki A, Shinohara M, Ikebe T, Nakamura S, Kurahara S, Garrod DR (1996) Immunohistochemical staining of desmosomal components in oral squamous cell carcinomas and its association with tumour behaviour. Br J Cancer 73:1491–1497PubMedGoogle Scholar
  16. 16.
    Hoschuetzky H, Aberle H, Kemler R (1994) Beta-catenin mediates the interaction of the cadherin–catenin complex with epidermal growth factor receptor. J Cell Biol 127:1375–1380PubMedCrossRefGoogle Scholar
  17. 17.
    Hynes RO (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25PubMedCrossRefGoogle Scholar
  18. 18.
    Iwai S, Katagiri W, Kong C, Amekawa S, Nakazawa M, Yura Y (2005) Mutations of the APC, beta-catenin, and axin 1 genes and cytoplasmic accumulation of beta-catenin in oral squamous cell carcinoma. J Cancer Res Clin Oncol 131:773–782PubMedCrossRefGoogle Scholar
  19. 19.
    Karayiannakis AJ, Nakopoulou L, Gakiopoulou H, Keramopoulos A, Davaris PS, Pignatelli M (2001) Expression patterns of beta-catenin in in situ and invasive breast cancer. Eur J Surg Oncol 27:31–36PubMedCrossRefGoogle Scholar
  20. 20.
    Krunic AL, Garrod DR, Madani S, Buchanan MD, Clark RE (1998) Immunohistochemical staining for desmogleins 1 and 2 in keratinocytic neoplasms with squamous phenotype: actinic keratosis, keratoacanthoma and squamous cell carcinoma of the skin. Br J Cancer 77:1275–1279PubMedGoogle Scholar
  21. 21.
    Krunic AL, Garrod DR, Smith NP, Orchard GS, Cvijetic OB (1996) Differential expression of desmosomal glycoproteins in keratoacanthoma and squamous cell carcinoma of the skin: an immunohistochemical aid to diagnosis. Acta Derm-Venereol 76:394–398PubMedGoogle Scholar
  22. 22.
    Kurzen H, Munzing I, Hartschuh W (2003) Expression of desmosomal proteins in squamous cell carcinomas of the skin. J Cutan Pathol 30:621–630PubMedCrossRefGoogle Scholar
  23. 23.
    Natsugoe S, Nakashima S, Matsumoto M, Sakita H, Sakamoto F, Okumura H, Baba M, Yoshinaka H, Takao S, Aikou T (2002) Biologic and imaging diagnosis of lymph node metastasis in esophageal carcinoma. J Surg Oncol 81:25–32PubMedCrossRefGoogle Scholar
  24. 24.
    Nelson WJ, Nusse R (2004) Convergence of Wnt, beta-catenin, and cadherin pathways. Science 303:1483–1487PubMedCrossRefGoogle Scholar
  25. 25.
    Ochiai A, Akimoto S, Shibata T, Kanai Y, Shibata T, Oyama T, Hirohashi S (1994) c-erbB2 gene product associates with catenins in human cancer cells. Biochem Biophys Res Commun 205:73–78PubMedCrossRefGoogle Scholar
  26. 26.
    Peifer M, Berg S, Reynolds AB (1994) A repeating amino acid motif shared by proteins with diverse cellular roles. Cell 76:789–791PubMedCrossRefGoogle Scholar
  27. 27.
    Peifer M, McCrea PD, Green KJ, Wieschaus E, Gumbiner BM (1992) The vertebrate adhesive junction proteins beta-catenin and plakoglobin and the Drosophila segment polarity gene armadillo form a multigene family with similar properties. J Cell Biol 118:681–691PubMedCrossRefGoogle Scholar
  28. 28.
    Pindborg JJ, Reichart PA, Smith CJ, van der Waal I (1997) Histological typing of cancer and precancer of the oral mucosa. Springer, BerlinGoogle Scholar
  29. 29.
    Pirinen RT, Hirvikoski P, Johansson RT, Hollmen S, Kosma VM (2001) Reduced expression of alpha-catenin, beta-catenin, and gamma-catenin is associated with high cell proliferative activity and poor differentiation in non-small cell lung cancer. J Clin Pathol 54:391–395PubMedCrossRefGoogle Scholar
  30. 30.
    Pittella F, Katsube K, Takemura T, Hashimoto T, Kawano T, Garrod D, Takagi M (2001) Perinuclear and cytoplasmic distribution of desmoglein in esophageal squamous cell carcinomas. Pathol Res Pract 197:85–91PubMedCrossRefGoogle Scholar
  31. 31.
    Qiao Q, Ramadani M, Gansauge S, Gansauge F, Leder G, Beger HG (2001) Reduced membranous and ectopic cytoplasmic expression of beta-catenin correlate with cyclin D1 overexpression and poor prognosis in pancreatic cancer. Int J Cancer 95:194–197PubMedCrossRefGoogle Scholar
  32. 32.
    Saldanha G, Ghura V, Potter L, Fletcher A (2004) Nuclear beta-catenin in basal cell carcinoma correlates with increased proliferation. Br J Dermatol 151:157–164PubMedCrossRefGoogle Scholar
  33. 33.
    Sawa Y, Kuroshima S, Yamaoka Y, Yoshida S (2005) Intracellular distribution of desmoplakin in human odontoblasts. J Histochem Cytochem 53:1099–1108PubMedCrossRefGoogle Scholar
  34. 34.
    Shinohara M, Hiraki A, Ikebe T, Nakamura S, Kurahara S, Shirasuna K, Garrod DR (1998) Immunohistochemical study of desmosomes in oral squamous cell carcinoma: correlation with cytokeratin and E-cadherin staining, and with tumour behaviour. J Pathol 184:369–381PubMedCrossRefGoogle Scholar
  35. 35.
    Su LK, Vogelstein B, Kinzler KW (1993) Association of the APC tumour suppressor protein with catenins. Science 262:1734–1737PubMedCrossRefGoogle Scholar
  36. 36.
    Williams HK, Sanders DS, Jankowski JA, Landini G, Brown AM (1998) Expression of cadherins and catenins in oral epithelial dysplasia and squamous cell carcinoma. J Oral Pathol Med 27:308–317PubMedCrossRefGoogle Scholar
  37. 37.
    Yeh KT, Chang JG, Lin TH, Wang YF, Chang JY, Shih MC, Lin CC (2003) Correlation between protein expression and epigenetic mutation changes of Wnt pathway-related genes in oral cancer. Int J Oncol 23:1001–1007PubMedGoogle Scholar
  38. 38.
    Yin T, Green KJ (2004) Regulation of desmosome assembly and adhesion. Semin Cell Dev Biol 15:665–677PubMedCrossRefGoogle Scholar
  39. 39.
    Zhurinsky J, Shtutman M, Ben-Ze'ev A (2000) Plakoglobin and beta-catenin: protein interactions, regulation and biological roles. J Cell Sci 113:3127–3131PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Lihong Wang
    • 1
    • 2
  • Tingjiao Liu
    • 3
  • Yao Wang
    • 1
  • Lei Cao
    • 4
  • Mai Nishioka
    • 2
  • Rodelio L. Aguirre
    • 2
  • Ayataka Ishikawa
    • 5
  • Li Geng
    • 1
  • Norihiko Okada
    • 2
  1. 1.Department of Bioengineering, School of sciencesGraduate School of Northeastern UniversityShenyangChina
  2. 2.Department of Diagnostic Oral Pathology, Oral Restitution,Oral health SciencesGraduate School of Tokyo Medical and Dental UniversityTokyoJapan
  3. 3.Sectiont of Oral Pathology, College of StomatologyDalian Medical UniversityDalianChina
  4. 4.Department of Oral Pathology, Oral Restitution, Oral health SciencesGraduate School of Tokyo Medical and Dental UniversityTokyoJapan
  5. 5.Department of Pathology, School of MedicineTokyo Women’s Medical UniversityTokyoJapan

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