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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Authors: | Steffen Rickelt Werner W Franke Yvette Doerflinger Sergij Goerdt Johanna M Brandner Wiebke K Peitsch |
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Institution: | (1) Helmholtz Group for Cell Biology, German Cancer Research Center, Heidelberg, Germany;(2) Department of Dermatology, University Hospital Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135 Mannheim, Germany;(3) Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany |
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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.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
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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Keywords: | Melanocyte Melanoma Cell-cell junctions Cadherins Desmogleins |
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