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Differentielle Veränderungen epidermaler Integrinmuster in Modellepithelien transformierter benigner und maligner Keratinozyten (HACAT-RAS)

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Wundheilung — Wundverschluß

Part of the book series: Fortschritte der operativen und onkologischen Dermatologie ((OP.DERMATOLOGIE,volume 8))

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Zusammenfassung

Aufgrund ihrer Bedeutung für Gewebestrukturierung und Interaktion mit extrazellulärer Matrix (ECM) wurden die Integrinmuster normaler Human-Keratinozyten, der gut differenzierenden Zellinie HaCaT, sowie von benignen und malignen HaCaT-ras Zellklonen analysiert. Vergleichbar zu Epidermis und Transplantaten normaler Zellen (auf thymus-aplastischen Nacktmäusen) war die Lokalisation der Integrine α2βl und α3βl (Immunfluoreszenz) in Epithelien von HaCaT und benignen Zellen perizellulär und weitgehend auf die Basalzellschicht beschränkt, während α6β4 größtenteils eine polare Verteilung assoziiert mit Basalmembrankomponenten zeigte. Dagegen kam es in Transplantaten maligner Zellen zu einer drastischen Expansion aller Integrine weit in suprabasale Bereiche mit gelegentlich fokal stark erhöhter Konzentration von α6β4. Diese Veränderungen waren auch in organotypischen Kokulturen maligner Zellen mit Fibroblasten manifest und dabei strikt abhängig von vitalen Funktionen der Mesenchymzellen. Die negative Korrelation der Integrinmuster mit dem Differenzierungsgrad und die verstärkte Expression in invasiven Bereichen unter Verlust der Zellpolarität deuten auf ursächliche Zusammenhänge mit malignem Wachstumsverhalten hin.

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Literatur

  1. Asselineau D, Dale BA, Bernard BA (1990) Filaggrin production by cultured human epidermal keratinocytes and its regulation by retinoic acid. Differentiation 45: 221–229

    Article  PubMed  CAS  Google Scholar 

  2. Beckerle MC (1990) The adhesion plaque protein, talin, is phosphorylated in vivo in chicken embryo fibroblasts exposed to a tumor-promoting phorbol ester. Cell Reg 1: 227–236

    CAS  Google Scholar 

  3. Boukamp P, Petrusevska RT, Breitkreutz D, Hornung J, Markham A, Fusenig NE (1988) Normal keratinization in a spontaneously immortalized aneupoloid keratinocyte cell line. J Cell Biol 106:761–771

    Google Scholar 

  4. Boukamp P, Stanbridge EJ, Foo DY, Cerutti PA, Fusenig NE (1990b) c-Ha-ras oncogene expression in immortalized human keratinocytes ( HaCaT) alters growth potential in vivo but lacks correlation with malignancy. Cancer Res 50: 2840–2847

    Google Scholar 

  5. Boukamp P, Fusenig NE (1993) „Trans-differentiation“ from epidermal to mesenchymal/myogenic phenotype is associated with a drastic change in cell-cell and cell-matrix adhesion molecules. J Cell Biol 120: 981–993

    Google Scholar 

  6. Brands R, De Boer A, Feltkamp CA, Roos E (1990) Disintegration of adhesion plaques in chicken embryo fibroblasts upon rous sarcoma virus-induced transformation: different dissociation rates for talin and vinculin. Exp Cell Res 186: 138–148

    Article  PubMed  CAS  Google Scholar 

  7. Breitkreutz D, Hornung J, Pöhlmann J, Brown-Biermann L, Bohnert A, Bowden PE, Fusenig NE (1986) Environmental induction of differentiation-specific keratins in malignant mouse. keratinocyte cell lines. Eur J Cell Biol 42: 255–267

    PubMed  CAS  Google Scholar 

  8. Breitkreutz D, Boukamp P, Stark H-J, Ryle C, Fusenig NE (1989) Response of established keratinocyte lines to modulators of epidermal differentiation. In: Reichert U, Shroot B (eds) Pharmacology and the skin, vol 3. Karger, Basel, pp 8–14

    Google Scholar 

  9. Breitkreutz D, Boukamp P, Ryle C, Stark H-J, Roop D, Fusenig NE (1991) Epidermal morphogenesis and keratin expression in c-Ha-ras-transfected tumorigenic clones of the human HaCaT cell line. Cancer Res 51: 4402–4409

    PubMed  CAS  Google Scholar 

  10. Breitkreutz D, Stark H-J, Plein P, Baur M, Fusenig NE (1993) Differential modulation of epidermal keratinization in immortalized (HaCaT) and tumorigenic human skin keratinocytes (HaCaT-ras) by retinoic acid and extracellular Ca2+. Differentiation 54: 201–217

    Article  PubMed  CAS  Google Scholar 

  11. Carter WG, Wayner EA, Bouchard TS, Kaur P (1990) The role of integrins a2ßl and oc3ßl in cell-cell and cell substrate adhesion of human epidermal cells. J Cell Biol 110: 1387–1404

    Article  PubMed  CAS  Google Scholar 

  12. Fuchs E (1990) Epidermal differentiation: the bare essentials. J Cell Biol 111: 2807–2814

    Article  PubMed  CAS  Google Scholar 

  13. Fusenig NE, Breitkreutz D, Boukamp P, Bohnert A, Mackenzie IC (1991) Epithelial-mesenchymal interactions in tissue homeostasis and malignant transformation. In: Johnson NW (ed) Risk markers of oral disease, 2: Oral Cancer. Cambridge University Press, Cambridge, pp 218–256

    Google Scholar 

  14. Kajiji S, Tamura RN, Quaranta V (1989) A novel integrin (Eß4) from human epithelial cells suggests a fourth family of integrin adhesion receptors. EMBO J 8: 673–680

    PubMed  CAS  Google Scholar 

  15. Klein CE, Steinmayer T, Kaufmann D, Weber L, Bröcker E–B (1991 a) Identification of a melanoma progression antigen as integrin VLA-2. J Invest Dermatol 96: 281–284

    Google Scholar 

  16. Klein CE, Dressel D, Steinmayer T, Mauch C, Eckes B, Krieg T, Bankert RB, Weber L (1991 b) Integrin oc2ßl is upregulated in fibroblasts and highly aggressive melanoma cells in three-dimensional collagen lattices and mediates the reorganization of collagen I fibrils. J Cell Biol 115: 1427–1436

    Google Scholar 

  17. Konter J, Kellner I, Klein E, Kaufmann R, Mielke V, Sterry W (1989) Adhesion molecule mapping in normal human skin. Arch Dermatol Res 281: 454–162

    Article  PubMed  CAS  Google Scholar 

  18. Limat A, Breitkreutz D, Hunziker T, Boillat C, Wiesmann U, Klein E, Noser F, Fusenig NE (1991) Restoration of the epidermal phenotype by follicular outer root sheath cells in recombinant culture with dermal fibroblasts. Exp Cell Res 194: 218–227

    Article  PubMed  CAS  Google Scholar 

  19. Marchisio PC, Bondanza S, Cremona O, Cancedda R, De Luca M (1991) Polarized expression of integrin receptors (oc6ß4, ot2ßl, oc3ßl, ocVß5) and their relationship with the cytoskeleton and basement membrane matrix in cultured human keratinocytes. J Cell Biol 112: 761–773

    Article  PubMed  CAS  Google Scholar 

  20. Nicholson LJ, Watt FM (1991) Decreased expression of fibronectin and the oc5ßl integrin during terminal differentiation of human keratinocytes. J Cell Sei 78: 225–232

    Google Scholar 

  21. Ryle CM, Breitkreutz D, Stark H-J, Leigh IM, Steinert PM, Roop D, Fusenig NE (1989) Density-dependent modulation of synthesis of keratins 1 and 10 in the human keratinocyte cell line HaCaT and in ras-transfected tumorigenic clones. Differentiation 40: 42–54

    Article  PubMed  CAS  Google Scholar 

  22. Scharffetter-Kochanek K, Klein CE, Heinen G, Mauch C, Schaefer T, Adelmann-Grill BC, Goerz G, Fusenig NE, Krieg TM, Plewig G (1992) Migration of a human keratinocyte cell line (HaCaT) to interstitial collagen type I is mediated by the a2ßl-integrin receptor. J Invest Dermatol 98: 3–11

    Article  PubMed  CAS  Google Scholar 

  23. Schwarz MA, Owaribe K, Kartenbeck J, Franke WW (1990) Desmosomes and hemidesmosomes: constitutive molecular components. Ann Rev Cell Biol 6: 461–491

    Article  PubMed  CAS  Google Scholar 

  24. Smola H, Thiekötter G, Fusenig NE (1993) Mutual induction of growth factor gene expression by epidermal-dermal cell interaction. J Cell Biol 122: 417–429

    Article  PubMed  CAS  Google Scholar 

  25. Sonnenberg A, Calafat J, Janssen H, Daams H, Van der Raaij-Helmer LMH, Falcioni R, Kennel SJ, Aplin JD, Baker J, Loizidou M, Garrod D (1991) Integrin oc6ß4 complex is located in hemidesmosomes, suggesting a major role in epidermal cell-basement membrane adhesion. J Cell Biol 113: 907–917

    CAS  Google Scholar 

  26. Takeichi M (1990) Cadherins: a molecular family important in selective cell-cell adhesion. Ann Rev Biochem 59: 237–252

    Article  PubMed  CAS  Google Scholar 

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© 1994 Springer-Verlag Berlin Heidelberg

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Breitkreutz, D., Stark, HJ., Baur, M., Fusenig, N.E. (1994). Differentielle Veränderungen epidermaler Integrinmuster in Modellepithelien transformierter benigner und maligner Keratinozyten (HACAT-RAS). In: Mahrle, G., Schulze, HJ., Krieg, T. (eds) Wundheilung — Wundverschluß. Fortschritte der operativen und onkologischen Dermatologie, vol 8. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79173-4_5

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  • DOI: https://doi.org/10.1007/978-3-642-79173-4_5

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-79174-1

  • Online ISBN: 978-3-642-79173-4

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