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Subtypes of melanocytes and melanoma cells distinguished by their intercellular contacts: heterotypic adherens junctions, adhesive associations, and dispersed desmoglein 2 glycoproteins

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Abstract

In the tissue integration of melanocytes and melanoma cells, an important role is attributed to cell adhesion molecules, notably the cadherins. In cultured melanoma cells, we have previously described a more heterogeneous repertoire of cadherins than normal, including some melanoma subtypes synthesizing the desmosomal cadherin, desmoglein 2, out of the desmosomal context. Using biochemical and immunological characterization of junctional molecules, confocal laser scanning, and electron and immunoelectron microscopy, we now demonstrate homo- and heterotypic cell-cell adhesions of normal epidermal melanocytes. In human epidermis, both in situ and in cell culture, melanocytes and keratinocytes are connected by closely aligned membranes that are interspersed by small puncta adhaerentia containing heterotypic complexes of E- and P-cadherin. Moreover, melanocytes growing in culture often begin to synthesize desmoglein 2, which is dispersed over extended areas of intimate adhesive cell-cell associations. As desmoglein 2 is not found in melanocytes in situ, we hypothesize that its synthesis is correlated with cell proliferation. Indeed, in tissue microarrays, desmoglein 2 has been demonstrated in a sizable subset of nevi and primary melanomas. The biological meanings of these cell-cell adhesion molecule arrangements, the possible diagnostic and prognostic significance of these findings, and the implications of the heterogeneity types of melanomas are discussed.

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Acknowledgements

We thank Martina Schnoelzer and Tore Kempf (Protein Analysis Facility, German Cancer Research Center) for performing the MALDI-TOF analyses.

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Authors and Affiliations

  1. Helmholtz Group for Cell Biology, German Cancer Research Center, Heidelberg, Germany

    Steffen Rickelt, Werner W. Franke, Yvette Doerflinger & Wiebke K. Peitsch

  2. Department of Dermatology, University Hospital Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135, Mannheim, Germany

    Yvette Doerflinger, Sergij Goerdt & Wiebke K. Peitsch

  3. Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany

    Johanna M. Brandner

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  1. Steffen Rickelt
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  2. Werner W. Franke
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Correspondence to Wiebke K. Peitsch.

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This work was supported in parts by grants from the Deutsche Forschungsgemeinschaft to W. K. Peitsch (project PE 896/1) and the Deutsche Krebshilfe to W. W. Franke (project 10-2049).

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Table S1

Survey of the results of the tissue microarrays of human melanomas and nevi: clinical data and detailed immunofluorescence microscopical results (− few or no reactive tumor cells, + 5%–24% reactive cells, ++ 25%–49% reactive cells, +++ 50%–74% reactive cells, ++++ more than 75% reactive cells, n.d. not done) (DOC 161 KB)

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Rickelt, S., Franke, W.W., Doerflinger, Y. et al. Subtypes of melanocytes and melanoma cells distinguished by their intercellular contacts: heterotypic adherens junctions, adhesive associations, and dispersed desmoglein 2 glycoproteins. Cell Tissue Res 334, 401–422 (2008). https://doi.org/10.1007/s00441-008-0704-7

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