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

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.

Insulin signaling via Akt2 switches plakophilin 1 functions from stabilizing cell adhesion to promoting cell proliferation

“…Interestingly, in actinic keratosis, a pre-cancerous lesion of the skin, as well as in oral squamous cell carcinoma (SCC) an elevated cytoplasmic pool of PKP1 has been reported (Kurzen et al, 2003;Narayana et al, 2010), supporting our notion that cytoplasmic PKP1 promotes proliferation. Although melanocytes typically do not express PKP1, some melanoma cell lines acquire PKP1 expression (Schmitt et al, 2007;Rickelt et al, 2008). A phospho-proteome screen of skin melanoma revealed PKP1 phosphorylation at several sites that we have identified here as Akt2 targets, namely S63, S65, S118, S121, S185 and S191 emphasizing the relevance of our findings in the context of tumor development (Zanivan et al, 2008).…”

Cordial connections: molecular ensembles and structures of adhering junctions connecting interstitial cells of cardiac valves in situ and in cell culture

“…Tissue samples and cultured cells were analysed by SDSpolyacrylamide gel electrophoresis (SDS-PAGE) and partly also by two-dimensional gel electrophoresis, followed by immunoblotting as previously described Wuchter et al 2007;Rickelt et al 2008). Relative proportions were estimated from stained and immunostained preparations (for vimentin and actin isoforms, notably smooth muscle-[sm-]α-actin, see also Franke et al 1979aFranke et al , b, 1980.…”

Discovering the Molecular Components of Intercellular Junctions--A Historical View

“…Therefore, it came as a surprise when it was recently noted that at least in some nonepithelial cell types (e.g., melanocytes and melanoma cells growing in culture, and melanoma cells in situ), a desmosomal glycoprotein, Dsg2, can occur as an abundant surface component out of any junctional complex (Schmitt et al 2007;Rickelt et al 2008).…”