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Vol. 38, No. 3, 2000
Issue release date: September 2000
Eur Urol 2000;38:331–338
(DOI:10.1159/000020302)

Alterations in Expression of Cadherin–6 and E–Cadherin during Kidney Development and in Renal Cell Carcinoma

Shimazui T. · Oosterwijk-Wakka J. · Akaza H. · Bringuier P.P. · Ruijter E. · Debruyne F.M.J. · Schalken J.A. · Oosterwijk E.
aDepartment of Urology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba–City, Ibaraki, Japan; bUrological Research Laboratory, and cDepartment of Pathology, University Hospital Nijmegen, The Netherlands

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Abstract

Objectives: Cell–cell adhesion mediated by cadherins is tight and stable and preserves tissue integrity. However, during tissue remodeling, e.g., development, adhesion may be modified for morphogenic movement. Similarly, during carcinogenesis, cell–cell adhesion might alter leading to a more aggressive phenotype. Here we describe cadherin expression patterns in developing, adult, and neoplastic kidney.

Methods: Fetal kidneys were obtained from voluntary terminations of pregnancy and 43 renal cell carcinomas (RCC) and normal kidneys were obtained at nephrectomy. Frozen sections of these specimens were stained immunohistochemically using antibodies against E–cadherin (ECD), cadherin–6 (CAD6) and α–catenin (α–cat).

Results: CAD6 was expressed in lower and middle limbs of the S–shaped bodies, structures that will develop into renal proximal tubules, which also express CAD6. Similarly, ECD was expressed in the upper limb of S–shaped bodies, structures which will develop into distal and collecting tubules which also express ECD. Twenty–four out of 43 RCC (55.8%) displayed a CAD6 (+)/ECD (–)/α–cat (+) phenotype. The other RCC had a CAD6 (+)/ECD (+)/α–cat (+) phenotype (10/43, 23.2%), CAD6 (–)/ECD (+)/α–cat (+) phenotype (3/43, 7.0%) or CAD6 (–)/ECD (–)/α–cat (+) phenotype (6/43, 14.0%), respectively. On the other hand, normal, heterogeneous, or absent expression of CAD6 was seen in 19, 15, and 9 tumors, whereas in 11, 2, and 30 tumors, respectively, ECD expression was seen. Survival curves showed that abnormal CAD6 expression correlated with a poor prognosis rather than abnormal ECD expression.

Conclusions: The combination of cadherin expression appeared to be fixed relatively early during kidney organogenesis. Since almost all RCC originate from proximal tubular epithelial cells (CAD6 (+)/ECD (–)/α–cat (+)), only 55.8% of RCC retained the original cadherin phenotype. Alterations in expression of these molecules may be a reflection of the degree of dedifferentiation from the primary organ. In addition, scoring of expression patterns including heterogeneous expression could be a useful tool to estimate the malignancy potential of the tumor.



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References

  1. Nagafuchi A, Takeichi M: Cell binding function of E–cadherin is regulated by the cytoplasmic domain. EMBO J 1988;7:3679–3684.
  2. Watabe M, Nagafuchi A, Tsukita S, Takeichi M: Induction of polarized cell–cell association and retardation of growth by activation of the E–cadherin–catenin adhesion system in a dispersed carcinoma line. J Cell Biol 1994;127: 247–256.
  3. Kawanishi J, Kato K, Sasaki K, Fujii S, Watanabe N, Niitsu Y: Loss of E–cadherin–dependent cell–cell adhesion due to mutation of the β–catenin gene in a human cancer cell line, HSC–39. Mol Cell Biol 1995;15:1175–1181.

    External Resources

  4. Nouwen EJ, Dauwe S, Van der Biest I, De Broe ME: Stage– and segment–specific expression of cell–adhesion molecules N–CAM, A–CAM and L–CAM in the kidney. Kidney Int 1993;44:147–158.
  5. Shimazui T, Giroldi LA, Bringuier PP, Oosterwijk E, Schalken JA: Complex cadherin expression in renal cell carcinoma. Cancer Res 1996;56:3234–3237.
  6. Xiang Y–Y, Tanaka M, Suzuki M, Igarashi H, Kiyokawa E, Naito Y, Ohtawara Y, Shen Q, Sugimura H, Kino I: Isolation of complementary DNA encoding K–cadherin, a novel rat cadherin preferentially expressed in fetal kidney and kidney carcinoma. Cancer Res 1994; 54:3034–3041.

    External Resources

  7. Shimoyama Y, Gotoh M, Terasaki T, Kitajima M, Hirohashi S: Isolation of sequence analysis of human cadherin–6 complementary DNA for the full coding sequence and its expression in human carcinoma cells. Cancer Res 1995;55: 2206–2211.

    External Resources

  8. Shimazui T, Bringuier PP, van Berkel H, Ruijter E, Akaza H, Debruyne FMJ, Oosterwijk E, Schalken J: Decreased expression of a–catenin is associated with poor prognosis of patients with localized renal cell carcinoma. Int J Cancer 1997;74:523–528.
  9. Mostofi FK: Histological typing of kidney tumours. International Histological Classification of Tumours, No. 25. World Health Organization, Geneva, 1982.
  10. International Union against Cancer TNM classification (kidney); in Sobin LH, Wittekind C (eds): TNM Classification of Malignant Tumors, ed 5. New York, Wiley, 1997, pp 180– 182.
  11. Shimazui T, Schalken JA, Giroldi LA, Jansen CFJ, Akaza H, Koiso K, Debruyne FMJ, Bringuier PP: Prognostic value of cadherin– associated molecules (α–, β– and γ–catenins and p120cas) in bladder tumors. Cancer Res 1996;56:4154–4158.
  12. Oosterwijk E, Ruiter J, Wakka JC, HuiskensvD, Meij JW, Jonas U, Fleuren G–J, Zwartendijk J, Hoedemaeker Ph, Warnaar SO: Immunohistochemical analysis of monoclonal antibody to renal antigens. Application in the diagnosis of renal cell carcinoma. Am J Pathol 1986;123:301–309.

    External Resources

  13. Shimazui T, Oosterwijk E, Akaza H, Bringuier PP, Ruijter E, van Berkel H, Oosterwijk–Wakka J, van Bokhoven A, Debruyne FMJ, Schalken JA: Expression of cadherin–6 as a novel diagnostic tool to predict prognosis of patients with E–cadherin–absent renal cell carcinoma. Clin Cancer Res 1998;4:2419–2424.
  14. Oosterwijk E, Van Muijen GN, OosterwijkWakka JC, Warnaar SO: Expression of intermediate–sized filaments in developing and adult human kidney and in renal cell carcinoma. J Histochem Cytochem 1990;38:385–392.
  15. Cho EA, Patterson LT, Brookhiser WT, Mah S, Kintner C, Dressler GR: Differential expression and function of cadherin–6 during renal epithelium development. Development 1998; 125:803–812.
  16. Piepenhagen PA, Nelson WJ: Differential expression of cell–cell and cell–substratum adhesion protein along the kidney nephron. Am J Physiol 1995;269:C1433–C1449.

    External Resources

  17. Katagiri A, Watanabe R, Tomita Y: E–cadherin expression in renal cell cancer and its significance in metastasis and survival. Br J Cancer 1995;71:376–379.

    External Resources

  18. Holthofer H, Miettinen A, Paasivuo R, Lehto V–P, Linder E, Alfthan O, Virtanen I: Cellular origin and differentiation of renal carcinomas. A fluorescence microscopic study with kidneyspecific antibodies, anti–intermediate filament antibodies, and lectins. Lab Invest 1983; 49:317–326.

    External Resources

  19. Bander NH, Finstad CL, Cordon–Cardo C, Ramsawak RD, Vaughan ED Jr, Whitmore WF Jr, Oettgen HF, Melamed MR, Old LJ: Analysis of a mouse monoclonal antibody that reacts with a specific region of the human proximal tubule and subsets renal cell carcinoma. Cancer Res 1989;49:6774–6780.
  20. Moll R, Hage C, Thoenes W: Expression of intermediate filament proteins in fetal and adult human kidney: Modulations of intermediate filament patterns during development and in damaged tissue. Lab Invest 1991;65:74–86.
  21. Vleminckx K, Vakaet L Jr, Mareel M, Fiers W, van Roy F: Genetic manipulation of E–cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell 1991; 66:107–119.
  22. Frixen UH, Behrens J, Sachs M, Eberle G, Voss B, Warda A, Lochner D, Birchmeier W: E–cadherin–mediated cell–cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol 1991;113:173–185.
  23. Oka H, Shiozaki H, Kobayashi K, Inoue M, Tahara H, Kobayashi T, Takatsuka Y, Matsuyoshi N, Hirano S, Takeichi M, Mori T: Expression of E–cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res 1993;53:1696– 1701.
  24. Gunji N, Oda T, Todoroki T, Kanazawa N, Kawamoto T, Yuzawa K, Scarpa A, Fukao K: Pancreatic carcinoma correlation between Ecadherin and a–catenin expression status and liver metastasis. Cancer 1998;82:1649–1656.
  25. Paul R, Ewing CM, Robinson JC, Marshall FF, Johnson KR, Wheelock MJ, Isaacs WB: Cadherin–6, a cell adhesion molecule specifically expressed in the proximal renal tubule and renal cell carcinoma. Cancer Res 1997;57:2741– 2748.
  26. Thoenes W, Storkel S, Rumpelt HJ: Histopathology and classification of renal cell tumors (adenomas, oncocytomas and carcinomas). The basic cytological and histopathological elements and their use for diagnostics. Pathol Res Pract 1986;181:125–143.
  27. Thoenes W, Storkel S, Rumpelt HJ, Moll R: Cytomorphological typing of renal cell carcinoma – a new approach. Eur Urol 1990;18 (suppl 2):6–9.


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