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Characterization of a novel type of adherens junction in meningiomas and the derived cell line HBL-52

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Abstract

Adhering junctions are generally grouped into desmosomes and adherens junctions based on their ultrastructural appearance and molecular composition. The armadillo-protein plakoglobin is common to both types of junctions, which are otherwise composed of mutually exclusive proteins. This view is based on observations in epithelial tissues but cannot easily be transferred to other cell types and tissues, as has become apparent during the last decade with the identification of new junctional proteins and the investigation of further non-epithelial junctions. Using a broad array of well-characterized specific antibodies against key junctional proteins in immunoblot reactions, high-resolution double-label laser scanning confocal microscopy, and immunoelectron microscopy, we describe a new type of adherens junction in human meningiomas and the human meningioma cell line HBL-52. This novel junction has a unique composition of proteins not found in any other tissue; it contains the desmosomal armadillo-protein plakophilin 2 together with the classic proteins of “epithelial” adherens junctions, i.e., E-cadherin (in some instances replaced by N-cadherin), alpha-catenin, beta-catenin, plakoglobin, and p120ctn. Ultrastructurally, it is formed between two or three neighboring cells. For pragmatic reasons, we suggest the name “meningeal junction” for this new structure.

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References

  • Akat K, Mennel HD, Kremer P, Gassler N, Bleck CK, Kartenbeck J (2003) Molecular characterization of desmosomes in meningiomas and arachnoidal tissue. Acta Neuropathol (Berl) 106:337–347

    Article  CAS  Google Scholar 

  • Baia GS, Slocum AL, Hyer JD, Misra A, Sehati N, VandenBerg SR, Feuerstein BG, Deen DF, McDermott MW, Lal A (2006) A genetic strategy to overcome the senescence of primary meningioma cell cultures. J Neurooncol 78:113–121

    Article  PubMed  CAS  Google Scholar 

  • Borrmann CM, Mertens C, Schmidt A, Langbein L, Kuhn C, Franke WW (2000) Molecular diversity of plaques of epithelial-adhering junctions. Ann N Y Acad Sci 915:144–150

    Article  PubMed  CAS  Google Scholar 

  • Borrmann CM, Grund C, Kuhn C, Hofmann I, Pieperhoff S, Franke WW (2006) The area composita of adhering junctions connecting heart muscle cells of vertebrates. II. Colocalizations of desmosomal and fascia adhaerens molecules in the intercalated disk. Eur J Cell Biol 85:469–485

    Article  PubMed  CAS  Google Scholar 

  • 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 277:10512–10522

    Article  PubMed  CAS  Google Scholar 

  • Choi HJ, Weiss WI (2004) Structural aspects of adherens junctions and desmosomes. In: Behrens J, Nelson WJ (ed) Handbook of experimental pharmacology, vol 165. Cell adhesion. Springer, Berlin, pp 23–65

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Dalal D, Molin LH, Piccini J, Tichnell C, James C, Bomma C, Prakasa K, Towbin JA, Marcus FI, Spevak PJ, Bluemke DA, Abraham T, Russell SD, Calkins H, Judge DP (2006) Clinical features of arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in plakophilin-2. Circulation 113:1641–1649

    Article  PubMed  CAS  Google Scholar 

  • Farquhar MG, Palade GE (1963) Junctional complexes in various epithelia. J Cell Biol 17:375–412

    Article  PubMed  CAS  Google Scholar 

  • Figarella-Branger D, Pellissier JF, Bouillot P, Bianco N, Mayan M, Grisoli F, Rougon G (1994) Expression of neural cell-adhesion molecule isoforms and epithelial cadherin adhesion molecules in 47 human meningiomas: correlation with clinical and morphological data. Mod Pathol 7:752–761

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Franke WW, Borrmann CM, Grund C, Pieperhoff S (2006) The area composita of adhering junctions connecting heart muscle cells of vertebrates. I. Molecular definition in intercalated disks of cardiomyocytes by immunoelectron microscopy of desmosomal proteins. Eur J Cell Biol 85:69–82

    Article  PubMed  CAS  Google Scholar 

  • Gerull B, Heuser A, Wichter T, Paul M, Basson CT, McDermott DA, Lerman BB, Markowitz SM, Ellinor PT, MacRae CA, Peters S, Grossmann KS, Drenckhahn J, Michely B, Sasse-Klaassen S, Birchmeier W, Dietz R, Breithardt G, Schulze-Bahr E, Thierfelder L (2004) Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. Nat Genet 36:1162–1164

    Article  PubMed  CAS  Google Scholar 

  • Godsel LM, Getsios S, Huen AC, Green KJ (2004) Structural aspects of adherens junctions and desmosomes. In: Behrens J, Nelson WJ (ed) Handbook of experimental pharmacology, vol 165. Cell adhesion. Springer, Berlin, pp 137–193

    Google Scholar 

  • Green KJ, Gaudry CA (2000) Are desmosomes more than tethers for intermediate filaments? Nat Rev Mol Cell Biol 1:208–216

    Article  PubMed  CAS  Google Scholar 

  • Grossmann KS, Grund C, Huelsken J, Behrend M, Erdmann B, Franke WW, Birchmeier W (2004) Requirement of plakophilin 2 for heart morphogenesis and cardiac junction formation. J Cell Biol 167:149–160

    Article  PubMed  CAS  Google Scholar 

  • Gusek W (1962) Submikroskopische Untersuchungen als Beitrag zur Struktur und Onkologie der Meningeome. Beitr Pathol Anat 127:274–326

    PubMed  CAS  Google Scholar 

  • Hämmerling B, Grund C, Boda-Heggemann J, Moll R, Franke WW (2006) The complexus adhaerens of mammalian lymphatic endothelia revisited: a junction even more complex than hitherto thought. Cell Tissue Res 324:55–67

    Article  PubMed  Google Scholar 

  • Hatta K, Takeichi M (1986) Expression of N-cadherin adhesion molecules associated with early morphogenetic events in chick development. Nature 320:447–449

    Article  PubMed  CAS  Google Scholar 

  • Hatzfeld M, Nachtsheim C (1996) Cloning and characterization of a new armadillo family member, p0071, associated with the junctional plaque: evidence for a subfamily of closely related proteins. J Cell Sci 109:2767–2778

    PubMed  CAS  Google Scholar 

  • Hatzfeld M, Green KJ, Sauter H (2003) Targeting of p0071 to desmosomes and adherens junctions is mediated by different protein domains. J Cell Sci 116:1219–1233

    Article  PubMed  CAS  Google Scholar 

  • Hazan RB, Phillips GR, Qiao RF, Norton L, Aaronson SA (2000) Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis. J Cell Biol 148:779–790

    Article  PubMed  CAS  Google Scholar 

  • Kapprell HP, Cowin P, Franke WW (1987) Biochemical characterization of the soluble form of the junctional plaque protein, plakoglobin, from different cell types. Eur J Biochem 166:505–517

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Kartenbeck J, Haselmann U, Gassler N (2005) Synthesis of junctional proteins in metastasizing colon cancer cells. Eur J Cell Biol 84:417–430

    Article  PubMed  CAS  Google Scholar 

  • Kepes JJ (1961) Electron microscopic studies of meningiomas. Am J Pathol 39:499–510

    PubMed  CAS  Google Scholar 

  • Li G, Satyamoorthy K, Herlyn M (2001) N-cadherin-mediated intercellular interactions promote survival and migration of melanoma cells. Cancer Res 61:3819–3825

    PubMed  CAS  Google Scholar 

  • Louis DN, Scheithauer BW, Budka H, Deimling Av, Kepes JJ (2000) Meningeal tumors. In: Kleihues P, Cavenee WK (ed) World Health Organisation classification of tumours: pathology and genetics of tumours of the nervous system. IARC Press, Lyon, pp 176–184

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Müller J, Ritt DA, Copeland TD, Morrison DK (2003) Functional analysis of C-TAK1 substrate binding and identification of PKP2 as a new C-TAK1 substrate. EMBO J 22:4431–4442

    Article  PubMed  Google Scholar 

  • Napolitano L, Kyle R, Fischer ER (1963) Ultrastructure of meningiomas and the derivation and nature of their cellular components. Cancer 17:241

    Google Scholar 

  • Paffenholz R, Franke WW (1997) Identification and localization of a neurally expressed member of the plakoglobin/armadillo multigene family. Differentiation 61:293–304

    Article  PubMed  CAS  Google Scholar 

  • Paffenholz R, Kuhn C, Grund C, Stehr S, Franke WW (1999) The arm-repeat protein NPRAP (neurojungin) is a constituent of the plaques of the outer limiting zone in the retina, defining a novel type of adhering junction. Exp Cell Res 250:452–464

    Article  PubMed  CAS  Google Scholar 

  • Puttmann S, Senner V, Braune S, Hillmann B, Exeler R, Rickert CH, Paulus W (2005) Establishment of a benign meningioma cell line by hTERT-mediated immortalization. Lab Invest 85:1163–1171

    Article  PubMed  CAS  Google Scholar 

  • Raimondi AJ, Mullan S, Evans JP (1962) Human brain tumors: an electron microscopic study. J Neurosurg 19:731–753

    Article  PubMed  CAS  Google Scholar 

  • Rose O, Grund C, Reinhardt S, Starzinski-Powitz A, Franke WW (1995) Contactus adherens, a special type of plaque-bearing adhering junction containing M-cadherin, in the granule cell layer of the cerebellar glomerulus. Proc Natl Acad Sci USA 92:6022–6026

    Article  PubMed  CAS  Google Scholar 

  • Schmelz M, Franke WW (1993) Complexus adhaerentes, a new group of desmoplakin-containing junctions in endothelial cells: the syndesmos connecting retothelial cells of lymph nodes. Eur J Cell Biol 61:274–289

    PubMed  CAS  Google Scholar 

  • Schmelz M, Moll R, Kuhn C, Franke WW (1994) Complexus adhaerentes, a new group of desmoplakin-containing junctions in endothelial cells. II. Different types of lymphatic vessels. Differentiation 57:97–117

    Article  PubMed  CAS  Google Scholar 

  • Schmidt A, Heid HW, Schafer 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Schwechheimer K, Zhou L, Birchmeier W (1998) E-Cadherin in human brain tumours: loss of immunoreactivity in malignant meningiomas. Virchows Arch 432:163–167

    Article  PubMed  CAS  Google Scholar 

  • Staehelin LA (1974) Structure and function of intercellular junctions. Int Rev Cytol 39:191–283

    Article  PubMed  CAS  Google Scholar 

  • Straub BK, Boda J, Kuhn C, Schnoelzer M, Korf U, Kempf T, Spring H, Hatzfeld M, Franke WW (2003) A novel cell-cell junction system: the cortex adhaerens mosaic of lens fiber cells. J Cell Sci 116:4985–4995

    Article  PubMed  CAS  Google Scholar 

  • Syrris P, Ward D, Asimaki A, Sen-Chowdhry S, Ebrahim HY, Evans A, Hitomi N, Norman M, Pantazis A, Shaw AL, Elliott PM, McKenna WJ (2006) Clinical expression of plakophilin-2 mutations in familial arrhythmogenic right ventricular cardiomyopathy. Circulation 113:356–364

    Article  PubMed  CAS  Google Scholar 

  • Tohma Y, Yamashima T, Yamashita J (1992) Immunohistochemical localization of cell adhesion molecule epithelial cadherin in human arachnoid villi and meningiomas. Cancer Res 52:1981–1987

    PubMed  CAS  Google Scholar 

  • Utsuki S, Oka H, Sato Y, Kawano N, Tsuchiya B, Kobayashi I, Fujii K (2005) Invasive meningioma is associated with a low expression of E-cadherin and beta-catenin. Clin Neuropathol 24:8–12

    PubMed  CAS  Google Scholar 

  • Wheelock MJ, Johnson KR (2003) Cadherins as modulators of cellular phenotype. Annu Rev Cell Dev Biol 19:207–235

    Article  PubMed  CAS  Google Scholar 

  • Yamashima T, Tohma Y, Yamashita J (1992) Expression of cell adhesion molecule E-cadherin in human arachnoid villi. J Neurosurg 77:749–756

    PubMed  CAS  Google Scholar 

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Acknowledgements

We gratefully acknowledge the interest and support of Prof. W.W. Franke and especially thank Dr. H. Spring for help with the confocal laser scanning microscopy, and E. Noffz for expert technical assistance (all German Cancer Research Center, Heidelberg, Germany). We are grateful to Prof. Kunze and Dr. P. Kremer (Department of Neurosurgery, University of Heidelberg, Germany) for providing some of the meningiomas and to Prof. H.D. Mennel (Phillips University of Marburg, Germany) for providing and classifying most of the tissue specimens.

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Author notes

  1. Christopher K. E. Bleck

    Present address: Cell Biology and Biophysics Unit, Griffith Group, EMBL, 69117, Heidelberg, Germany

  2. Uta Haselmann-Weiss

    Present address: Electron Microscopy Core Facility, EMBL, 69117, Heidelberg, Germany

Authors and Affiliations

  1. Division of Cell Biology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany

    Kemal Akat, Christopher K. E. Bleck, Uta Haselmann-Weiss & Jürgen Kartenbeck

  2. Department of Cardiology, University Hospital Mannheim, Ruprecht Karls University Heidelberg, Mannheim, Germany

    Kemal Akat

  3. Department of Gastroenterology, University Hospital Heidelberg, Ruprecht Karls University Heidelberg, Heidelberg, Germany

    Young-Min Anna Lee

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  1. Kemal Akat
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Correspondence to Kemal Akat.

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All authors declare the absence of conflicts of interest.

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Akat, K., Bleck, C.K.E., Lee, YM.A. et al. Characterization of a novel type of adherens junction in meningiomas and the derived cell line HBL-52. Cell Tissue Res 331, 401–412 (2008). https://doi.org/10.1007/s00441-007-0512-5

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