Summary
Xenografting into nude mice forms a system for analysis of human tissues under experimental conditions. In this study, normal skin samples and basal cell carcinomas were investigated, prior to and after transplantation, using immunofluorescence methods with antibodies against keratins, laminin, and collagen type IV. Three groups of transplants were studied: (a) intact tissue samples, (b) human epithelium (either normal or neoplastic) recombined with normal human dermis and, (c) human epithelium recombined with normal mouse dermis. Transplants recovered after 3 weeks showed the following characteristics. 1) The xenograft system was satisfactory in terms of host survival and rate of successful tissue recovery except for recombinants between human epithelium and mouse dermis. 2) Intact and recombined samples of normal skin retained their preexisting patterns of architecture, cytodifferentiation, and basement membrane staining. 3) Solid nonfibrosing basal cell carcinomas showed altered architecture and differentiation of both the epithelium and the basement membrane zone after transplantation: the solid tumor pattern changed towards spreading of tumor cells, a more squamous differentiation pattern was apparent and was confirmed by reactivity with antibodies against large keratins. Discontinuities of the basement membrane zone were detected with antibodies against laminin and collagen type IV. These changes were seen in both intact and recombined tumor transplants.
Similar content being viewed by others
References
Bauer EZ, Gordon JM, Reddick ME, Eisen AZ (1977) Quantitation and immunocytochemical localization of human skin collagenase in basal cell carcinoma. J Invest Dermatol 69:363–367
De Moraga JM, Winkelmann RK, Jordon RE (1970) Immunofluorescence of epithelial skin tumors. Cancer 25:1404–1407
Doran TI, Vidrich A, Sun T-T (1980) Intrinsic and extrinsic regulation of the differentiation of skin, corneal and esophageal epithelial cells. Cell 22:17–25
Franke WW, Schiller DL, Moll R, Winter A, Schmid E, Engelbrecht I, Denk H, Krepler R, Platzer B (1981) Diversity of cytokeratins. Differentiation specific expression of cytokeratin polypeptides in epithelial cells and tissues. J Mol Biol 153:933–959
Fuchs E (1981) Evolution and complexity of the genes encoding the keratins of human epidermal cells. J Invest Dermatol 81:141s-144s
Grimwood RE, Huff JC, Harbell JW, Clark RAF (1984) Fibronectin in basal cell epithelioma: sources and significance. J Invest Dermatol 82:145–149
Grimwood RE, Johnson CA, Ferris CF, Mercill DB, Mellette JR, Huff JC (1985) Transplantation of human basal cell carcinomas to athymic nude mice. Cancer 56:519–523
Grimwood RE, Ferris CF, Mercill DB, Huff JC (1986) Proliferating cells of human basal cell carcinoma are located on the periphery of tumor nodules. J Invest Dermatol 86:191–194
Haftek M, Ortonne JP, Staquet MJ, Viac J, Thivolet J (1981) Normal and psoriatic human skin grafts on “nude” mice: morphological and immunochemical studies. J Invest Dermatol 76:48–52
Holmstrup P, Dabelsteen E, Reibel J, Harder F (1981) Normal keratinized mucosa transplants in nude mice. Acta Odontol Scand 39:187–193
Hundeiker M (1983) Die Basaliome. Aus der Sicht der Histologie. Ber Pathol 98:725–795
Jacobs GH, Rippey JJ, Altini M (1982) Prediction of aggressive behavior in basal cell carcinoma. Cancer 49:553–537
Kallioinen M, Autio-Harmainen H, Dammert K, Risteli J, Risteli L (1984) Discontinuity of the basement membrane in fibrosing basocellular carcinomas and basosquamous carcinomas of the skin: an immunohistochemical study with human laminin and type IV collagen antibodies. J Invest Dermatol 82:248–251
Lever WF, Schaumburg-Lever G (1983) Histopathology of the skin, 6th edn. Lippincott, Philadelphia, pp 562–575
Liotta LA, Rao CN, Barsky SH (1983) Tumor invasion and the extracellular matrix. Lab Invest 49:636–649
Löning T, Staquet MJ, Thivolet J, Seifert G (1980) Keratin polypeptides distribution in normal and diseased human epidermis and oral mucosa. Immunohistochemical study on unaltered epithelium and inflammatory premalignant and malignant lesions. Virchows Arch [A] 388:273–288
Mackenzie IC, Hill MW (1981) Maintenance of regionally specific patterns of cell proliferation and differentiation in transplanted skin and oral mucosa. Cell Tissue Res 219:597–607
Mackenzie IC, Hill MW (1984) Connective tissue influences on patterns of epithelial architecture and keratinization in skin and oral mucosa of the adult mouse. Cell Tissue Res 235:551–559
Mackenzie IC, Dabelsteen E, Roed-Petersen B (1979) A method for studying epithelial-mesenchymal interactions in human oral mucosal lesions. Scand J Dent Res 87:234–243
Martinez-Hernandez A, Amenta PS (1983) The basement membrane in pathology. Lab Invest 48:649–656
Moll R, Franke WW, Schiller DK, Geiger B, Krepler R (1982) The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:11–24
Moll R, Franke WW, Volc-Platzer B, Krepler R (1982) Different keratin polypeptides in epidermis and other epithelia of human skin: a specific cytokeratin of molecular weight 46,000 in epithelia of the pilosebaceous tract and basal cell epitheliomas. J Cell Biol 95:285–295
Moll R, Krepler R, Franke WW (1983) Complex cytokeratin polypeptide patterns observed in certain human carcinomas. Differentiation 23:256–269
Nelson DL, Little CK, Balian G (1983) Distribution of fibronectin and laminin in basal cell epitheliomas. J Invest Dermatol 80:446–452
Prunieras M, Regnier M, Fougere S, Woodley D (1983) Keratinocytes synthesize basal-lamina proteins in culture. J Invest Dermatol 81:74s-81s
Stanley JR, Beckwith JB, Fuller RP, Katz SI (1982) A specific antigenic defect of the basement membrane is found in basal cell carcinoma but not in other epidermal tumors. Cancer 50:1486–1490
Sun T-T, Eicher R, Nelson WG, Tseng SCG, Weiss RA, Jarvinen M, Woodcock-Mitchell J (1983) Keratin classes: molecular markers for different types of epithelial differentiation. J Invest Dermatol 81:109s-115s
Van Cauwenberge D, Pierard GE, Foidart JM, Lapiere CM (1983) Immunohistochemical localization of laminin, type IV and type V collagen in basal cell carcinoma. Br J Dermatol 108:163–170
Van Scott, EJ, Reinertson RP (1961) The modulating influence of stromal environment on epithelial cells studies in human autotransplants. J Invest Dermatol 36:109–131
Viac J, Reano A, Thivolet J (1982) Cytokeratins in human basal and squamous cell carcinomas: biochemical, immunohistological findings and comparisons with normal epithelia. J Cutan Pathol 9:377–390
Viac J, Reano A, Brochier J, Staquet MJ, Thivolet J (1983) Reactivity pattern of a monoclonal antikeratin antibody (KL1). J Invest Dermatol 81:351–354
Weber L, Krieg T, Muller PK, Kirsch E, Timpl R (1982) Immunofluorescent localization of type IV collagen and laminin in human skin and its application in junctional zone pathology. Br J Dermatol 106:267–273
Author information
Authors and Affiliations
Additional information
This study was supported by a grant from the Deutsche Forschungsgemeinschaft (Lo 285/2-2) and of the Hamburg Stiftung zur Förderung der Krebsbekämpfung (I 333), and the National Institutes of Health, NIDR RO1 DE05190
Rights and permissions
About this article
Cite this article
Löning, T.H., Mackenzie, I.C. Immunohistochemical studies of basal cell carcinomas transplanted into nude mice. Arch Dermatol Res 279, 37–43 (1986). https://doi.org/10.1007/BF00404356
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00404356