Homo‐ and heterotypic cell–cell contacts in Merkel cells and Merkel cell carcinomas: heterogeneity and indications for cadherin switching

Werling, Anna Maria; Doerflinger, Yvette; Brandner, Johanna M.; Fuchs, Franca; Becker, Jürgen C.; Schrama, David; Kurzen, Hjalmar; Goerdt, Sergij; Peitsch, Wiebke K.

doi:10.1111/j.1365-2559.2011.03748.x

Cited by 20 publications

(24 citation statements)

References 72 publications

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“…N-cadherin, known as an important member of the cadherin family that mediates calcium-dependent adhesion, is normally expressed in mesenchymal cells. Loss of E-cadherin and increased N-cadherin expression (E/N-cadherin switch) is now defined as a major hallmark of EMT [26], [27]. Snail, one member of the zinc finger family composed of a highly conserved COOH-terminal region, induces EMT and tumor invasion by binding the E-cadherin promoter through E-box sequences.…”

Section: Introductionmentioning

confidence: 99%

Embryonic Stem Cells Markers SOX2, OCT4 and Nanog Expression and Their Correlations with Epithelial-Mesenchymal Transition in Nasopharyngeal Carcinoma

et al. 2013

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Expression of embryonic stem cells (ESCs) markers (SOX2, OCT4, Nanog and Nestin) is crucial for progression of various human malignancies. The purpose of this study was to investigate the expression and prognostic impact of these molecules in nasopharyngeal carcinoma (NPC) patients by immunohistochemistry and immunofluorescence. In the present study, we found that the expression levels of SOX2, OCT4 and Nanog were highly expressed in NPC compared with the non-tumorous tissues. Furthermore, these proteins correlated significantly with several clinicalpathological factors and epithelial-mesenchymal transition (EMT)-associated indicators (E-cadherin/N-cadherin and Snail). In multivariate analyses, high expression of OCT4 (P = 0.013) and Nanog (P = 0.040), but not that of SOX2, was associated with worse survival and had strongly independent prognostic effects. Of note, OCT4 and Nanog were more frequently located at the invasive front of tumors, and correlated significantly with various aggressive behaviors including T classification, N classification, M classification and clinical stage. Furthermore, patients with co-expression of OCT4 and Nanog in the invasive front had significantly worse survival (P = 0.005). Interestingly, at the invasive front, these molecules correlated significantly with Nestin expression in endothelial cells (P<0.001). These findings provide evidence that ESCs biomarkers OCT4 and Nanog serves as independent prognostic factors for NPC. Additionally, cancer cells in the invasive front of NPC acquiring ESCs-like features should be maintained by vascular niches.

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Section: Introductionmentioning

confidence: 99%

Embryonic Stem Cells Markers SOX2, OCT4 and Nanog Expression and Their Correlations with Epithelial-Mesenchymal Transition in Nasopharyngeal Carcinoma

et al. 2013

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“…Scale bars: 0.2 μm (a, b) and 0.1 μm (c-e) various proliferatively transformed cell cultures of malignant "soft tissue tumors" (e.g., Barth et al 2009;Rickelt et al 2009Rickelt et al , 2010; for reviews see Franke et al 2009;Pieperhoff et al 2010). It seems surprising that Pkp2 has been detected so late as a highly MC-specific marker in the epidermis and its appendages and until very recently its presence in MC-keratinocytes has even been formally denied (e.g., Werling et al 2011). Our discovery of Pkp2 in MCs may partly be the result of a new generation of very sensitive Pkp2-antibodies, as is also suggested by recent findings in certain tumor cells and cell cultures (e.g., Barth et al 2009;Rickelt et al 2009Rickelt et al , 2010.…”

Section: Discussionmentioning

confidence: 98%

Intercellular adhering junctions with an asymmetric molecular composition: desmosomes connecting Merkel cells and keratinocytes

2011

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Merkel cells (MCs) are special neuroendocrine epithelial cells that occur as individual cells or as cell groups within the confinements of a major epithelium formed and dominated by other epithelial cells. In the epidermis and some of its appendages MCs are mostly located in the basal cell layer, occasionally also in suprabasal layers and generally occur in linear arrays in outer root sheath cell layers of hair follicles. As MCs are connected to the adjacent keratinocytes by a series of adhering junctions (AJs), of which the desmosomes are the most prominent, these junctions represent heterotypic cell-cell connections, i.e. a kind of structure not yet elucidated in molecular terms. Therefore, we have studied these AJs in order to examine the molecular composition of the desmosomal halves. Using light- and electron-microscopic immunolocalization and keratin 20 as the MC-specific cell type marker we show that the plaques of the MC half of the desmosomes specifically and constitutively contain plakophilin Pkp2. This protein, however, is absent in the keratinocyte half of such heterotypic desmosomes which instead contains Pkp1 and/or Pkp3. We discuss the developmental, tissue-architectonic and functional importance of such asymmetric junctions in normal physiology as well as in diseases, in particular in the formation of distant tumor cell metastasis.

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“…Alterations of TJ protein expression and localization have also been described in keratinocytic skin carcinomas , Merkel cell carcinomas and melanomas [ 18,33,62,63,78,94,117 ] . In a two-step mouse carcinogenesis model, Arabzadeh and coworkers [ 6 ] noted a downregulation of Cldn-1 in the basal cell layer and of Cldn-1, 6,-11, -12 and −18 in the lower suprabasal epidermal layers.…”

Section: Tjs and Tj Proteins In Skin Diseasesmentioning

confidence: 94%

The Role of Tight Junctions and Aquaporins in Skin Dryness

Brandner

2012

Treatment of Dry Skin Syndrome

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Homo‐ and heterotypic cell–cell contacts in Merkel cells and Merkel cell carcinomas: heterogeneity and indications for cadherin switching

Abstract: Assuming that MCCs originate from Merkel cells, our data indicate a switch from E- and P-cadherin to N-cadherin during tumorigenesis. Whether the unexpected heterogeneity of junctional proteins can be exploited for prognostic and therapeutic purposes will need to be examined.

Cited by 20 publications

References 72 publications

Embryonic Stem Cells Markers SOX2, OCT4 and Nanog Expression and Their Correlations with Epithelial-Mesenchymal Transition in Nasopharyngeal Carcinoma

Embryonic Stem Cells Markers SOX2, OCT4 and Nanog Expression and Their Correlations with Epithelial-Mesenchymal Transition in Nasopharyngeal Carcinoma

Intercellular adhering junctions with an asymmetric molecular composition: desmosomes connecting Merkel cells and keratinocytes

The Role of Tight Junctions and Aquaporins in Skin Dryness

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