Abstract
Intercellular junctions morphologically identical to epithelial desmosomes are known structures in meningiomas and arachnoidal tissue. Desmoplakin as one of the desmosomal plaque components has proven to be a reliable marker for diagnosis of meningeal tumors. Here we demonstrate by immunofluorescence microscopy, immunoblot and reverse transcription-PCR reactions that cells of arachnoidal tissue, of diverse meningioma subtypes and of a meningioma-derived cell line contain the full complement of the typical desmosomal proteins desmoplakin (DP), plakophilin 2 (PP2), desmocollin 2 (Dsc2) and desmoglein 2 (Dsg2). Consequently, all these molecules are suitable for diagnostic applications of meningioma tumors. In addition to these constitutive desmosomal components, representative for single-layered (simple) epithelia, the dural border cells of the arachnoid and about 60% of the meningiomas tested were positive for desmocollin 3 (Dsc3), a protein in epithelia taken as an indicator for differentiation.
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Achtstätter T, Hatzfeld M, Quinlan RA, Parmelee DC, Franke WW (1986) Separation of cytokeratin polypeptides by gel electrophoretic and chromatographic techniques and their identification by immunoblotting. Methods Enzymol 134:355–371
Amagai M, Klaus-Kovtun V, Stanley JR (1991) Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion. Cell 67:869–877
Behrens J (1999) Cadherins and catenins: role in signal transduction and tumor progression. Cancer Metastasis Rev 18:15–30
Buxton RS, Cowin P, Franke WW, Garrod DR, Green KJ, King IA, Koch PJ, Magee AI, Rees DA, Stanley JR (1993) Nomenclature of the desmosomal cadherins. J Cell Biol 121:481–483
Chidgey MA, Yue KK, Gould S, Byrne C, Garrod DR (1997) Changing pattern of desmocollin 3 expression accompanies epidermal organisation during skin development. Dev Dyn 210:315–327
Cho KG, Hoshino T, Nagashima T, Murovic JA, Wilson CB (1986) Prediction of tumor doubling time in recurrent meningiomas. Cell kinetics studies with bromodeoxyuridine labeling. J Neurosurg 65:790–794
Cowin P, Garrod DR (1983) Antibodies to epithelial desmosomes show wide tissue and species cross- reactivity. Nature 302:148–150
Cowin P, Kapprell HP, Franke WW, Tamkun J, Hynes RO (1986) Plakoglobin: a protein common to different kinds of intercellular adhering junctions. Cell 46:1063–1073
Erlandson RA (1981) Contribution of TEM to tumor diagnosis. In: Erlandson RA (ed) Diagnostic transmission electron microscopy of human tumors, Masson, New York, pp 125–128
Franke WW, Schmid E, Osborn M, Weber K (1978) Different intermediate-sized filaments distinguished by immunofluorescence microscopy. Proc Natl Acad Sci USA 75:5034–5038
Franke WW, Schmid E, Winter S, Osborn M, Weber K (1979) Widespread occurrence of intermediate-sized filaments of the vimentin-type in cultured cells from diverse vertebrates. Exp Cell Res 123:25–46
Franke WW, Schmid E, Grund C, Muller H, Engelbrecht I, Moll R, Stadler J, Jarasch ED (1981) Antibodies to high molecular weight polypeptides of desmosomes: specific localization of a class of junctional proteins in cells and tissue. Differentiation 20:217–241
Franke WW, Goldschmidt MD, Zimbelmann R, Mueller HM, Schiller DL, Cowin P (1989) Molecular cloning and amino acid sequence of human plakoglobin, the common junctional plaque protein. Proc Natl Acad Sci USA 86:4027–4031
Frederickson RG (1991) The subdural space interpreted as a cellular layer of meninges. Anat Rec 230:38–51
Gendler SJ (2001) MUC1, the renaissance molecule. J Mammary Gland Biol Neoplasia 6:339–353
Green KJ, Gaudry CA (2000) Are desmosomes more than tethers for intermediate filaments? Nat Rev Mol Cell Biol 1:208–216
Haines DE (1991) On the question of a subdural space. Anat Rec 230:3–21
Haines DE, Harkey HL, al Mefty O (1993) The "subdural" space: a new look at an outdated concept. Neurosurgery 32:111–120
Heid HW, Schmidt A, Zimbelmann R, Schäfer S, Winter-Simanowski S, Stumpp S, Keith M, Figge U, Schnolzer M, Franke WW (1994) Cell type-specific desmosomal plaque proteins of the plakoglobin family: plakophilin 1 (band 6 protein). Differentiation 58:113–131
Ho KL (1980) Primary meningioma of the nasal cavity and paranasal sinuses. Cancer 46:1442–1447
Kapprell HP, Owaribe K, Franke WW (1988) Identification of a basic protein of Mr 75,000 as an accessory desmosomal plaque protein in stratified and complex epithelia. J Cell Biol 106:1679–1691
Kartenbeck J, Schwechheimer K, Moll R, Franke WW (1984) Attachment of vimentin filaments to desmosomal plaques in human meningiomal cells and arachnoidal tissue. J Cell Biol 98:1072–1081
Kepes JJ (1961) Electron microscopic studies of meningiomas. Am J Pathol 39:499–510
Kepes JJ (1962) Electron microscopic studies of meningiomas. In: Jacob H (ed) Proceedings of the 4th International Congress of Neuropathology, Munich, 1961. Thieme, Stuttgart
Kepes JJ (1982) Meningiomas: biology, pathology, and differential diagnosis. Masson, New York
Kleihues P, Cavenee WK (2000) World Health Organisation classification of tumours: pathology and genetics of tumours of the nervous system, IARC Press, Lyon
Koch PJ, Franke WW (1994) Desmosomal cadherins: another growing multigene family of adhesion molecules. Curr Opin Cell Biol 6:682–687
Koch PJ, Goldschmidt MD, Zimbelmann R, Troyanovsky R, Franke WW (1992) Complexity and expression patterns of the desmosomal cadherins. Proc Natl Acad Sci USA 89:353–357
Kolles H, Niedermayer I, Schmitt C, Henn W, Feld R, Steudel WI, Zang KD, Feiden W (1995) Triple approach for diagnosis and grading of meningiomas: histology, morphometry of Ki-67/Feulgen stainings, and cytogenetics. Acta Neurochir (Wien) 137:174–181
Lindblom A, Ruttledge M, Collins VP, Nordenskjold M, Dumanski JP (1994) Chromosomal deletions in anaplastic meningiomas suggest multiple regions outside chromosome 22 as important in tumor progression. Int J Cancer 56:354–357
Mertens C, Kuhn C, Franke WW (1996) Plakophilins 2a and 2b: constitutive proteins of dual location in the karyoplasm and the desmosomal plaque. J Cell Biol 135:1009–1025
Mertens C, Kuhn C, Moll R, Schwetlick I, Franke WW (1999) Desmosomal plakophilin 2 as a differentiation marker in normal and malignant tissues. Differentiation 64:277–290
Mueller H, Franke WW (1983) Biochemical and immunological characterization of desmoplakins I and II, the major polypeptides of the desmosomal plaque. J Mol Biol 163:647–671
Nabeshima S, Reese TS, Landis DM, Brightman MW (1975) Junctions in the meninges and marginal glia. J Comp Neurol 164:127–169
Nuber UA, Schäfer S, Schmidt A, Koch PJ, Franke WW (1995) The widespread human desmocollin Dsc2 and tissue-specific patterns of synthesis of various desmocollin subtypes. Eur J Cell Biol 66:69–74
Nuber UA, Schäfer S, Stehr S, Rackwitz HR, Franke WW (1996) Patterns of desmocollin synthesis in human epithelia: immunolocalization of desmocollins 1 and 3 in special epithelia and in cultured cells. Eur J Cell Biol 71:1–13
Parrish EP, Garrod DR, Mattey DL, Hand L, Steart PV, Weller RO (1986) Mouse antisera specific for desmosomal adhesion molecules of suprabasal skin cells, meninges, and meningioma. Proc Natl Acad Sci USA 83:2657–2661
Parrish EP, Steart PV, Garrod DR, Weller RO (1987) Antidesmosomal monoclonal antibody in the diagnosis of intracranial tumours. J Pathol 153:265–273
Peifer M, Wieschaus E (1990) The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin. Cell 63:1167–1176
Prayson RA (1996) Malignant meningioma: a clinicopathologic study of 23 patients including MIB1 and p53 immunohistochemistry. Am J Clin Pathol 105:719–726
Schäfer S, Koch PJ, Franke WW (1994) Identification of the ubiquitous human desmoglein, Dsg2, and the expression catalogue of the desmoglein subfamily of desmosomal cadherins. Exp Cell Res 211:391–399
Schmelz M, Duden R, Cowin P, Franke WW (1986) A constitutive transmembrane glycoprotein of Mr 165,000 (desmoglein) in epidermal and non-epidermal desmosomes. I. Biochemical identification of the polypeptide. Eur J Cell Biol 42:177–183
Schmelz M, Duden R, Cowin P, Franke WW (1986) A constitutive transmembrane glycoprotein of Mr 165,000 (desmoglein) in epidermal and non-epidermal desmosomes. II. Immunolocalization and microinjection studies. Eur J Cell Biol 42:184–199
Schmidt A, Heid HW, Schäfer S, Nuber UA, Zimbelmann R, Franke WW (1994) Desmosomes and cytoskeletal architecture in epithelial differentiation: cell type-specific plaque components and intermediate filament anchorage. Eur J Cell Biol 65:229–245
Schmidt A, Langbein L, Prätzel S, Rode M, Rackwitz HR, Franke WW (1999) Plakophilin 3—a novel cell-type-specific desmosomal plaque protein. Differentiation 64:291–306
Schnitt SJ, Vogel H (1986) Meningiomas. Diagnostic value of immunoperoxidase staining for epithelial membrane antigen. Am J Surg Pathol 10:640–649
Schwechheimer K, Kartenbeck J, Moll R, Franke WW (1984) Vimentin filament-desmosome cytoskeleton of diverse types of human meningiomas. A distinctive diagnostic feature. Lab Invest 51:584–591
Vilela MJ, Parrish EP, Wright DH, Garrod DR (1987) Monoclonal antibody to desmosomal glycoprotein 1—a new epithelial marker for diagnostic pathology. J Pathol 153:365–375
Wolff M, Rankow RM (1971) Meningioma of the parotid gland: an insight into the pathogenesis of extracranial meningiomas. Hum Pathol 2:453–459
Zotter S, Hageman PC, Lossnitzer A, Tweel J van den, Hilkens J, Mooi WJ, Hilgers J (1988) Monoclonal antibodies to epithelial sialomucins recognize epitopes at different cellular sites in adenolymphomas of the parotid gland. Int J Cancer Suppl 3:38–44
Acknowledgements
We gratefully acknowledge Prof. W.W. Franke's interest and support. We thank Dr. H. Spring for help with the confocal laser microscopy, Uta Haselmann, E. Noffz and R. Zimbelmann for expert technical assistance and A. Wohlfahrt for correcting the manuscript (all German Cancer Research Center).
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Akat, K., Mennel, HD., Kremer, P. et al. Molecular characterization of desmosomes in meningiomas and arachnoidal tissue. Acta Neuropathol 106, 337–347 (2003). https://doi.org/10.1007/s00401-003-0736-8
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DOI: https://doi.org/10.1007/s00401-003-0736-8