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Role of epithelial–mesenchymal transition involved molecules in the progression of cutaneous melanoma

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Abstract

Epithelial–mesenchymal transition (EMT) has been suggested to have a driving role in the acquisition of a metastatic potential by melanoma cells. Important hallmarks of EMT include both E-cadherin downregulation and increased expression of N-cadherin. This switch in distinct classes of adhesion molecules leads melanoma cells to lose contact with adjacent keratinocytes and interact instead with stromal fibroblasts and endothelial cells, thus promoting dermal and vascular melanoma invasion. Consequently, tumor cells migrate to distant host tissues and establish metastases. A key regulator in the induction of EMT in melanoma is the Notch1 signaling pathway that, when activated, is prompt to upregulate N-cadherin expression. By means of this strategy, melanoma cells gain enhanced survival, proliferation and invasion properties, driving the tumor toward a more aggressive phenotype. On the basis of these statements, the present study aimed to investigate the possible association between N-cadherin and Notch1 presence in primary cutaneous melanomas and lymph node metastases. Our results from immunohistochemical analysis confirmed a positive correlation between N-cadherin and Notch1 presence in the same tumor samples. Moreover, this study highlighted that a concomitant high expression of N-cadherin and Notch1, both in primary lesions and in lymph node metastases, predicts an adverse clinical outcome in melanoma patients. Therefore, N-cadherin and Notch1 co-presence can be monitored as a predictive factor in early- and advanced-stage melanomas and open additional therapeutic targets for the restraint of melanoma metastasis.

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Acknowledgements

The study was funded by grants from the “Fondazione Banco di Sardegna” (FBS) and from the “Fondo Integrativo per la Ricerca” (FIR) of the University of Cagliari, Italy.

Particular thanks are due to Mrs. Itala Mosso for her expert technical assistance.

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Author notes

  1. Daniela Murtas and Cristina Maxia share equal contribution.

Authors and Affiliations

  1. Department of Biomedical Sciences, Section of Cytomorphology, University of Cagliari, Cittadella Universitaria, S.P. 8, Monserrato, 09042, Cagliari, Italy

    Daniela Murtas, Cristina Maxia, Andrea Diana, Claudia Corda, Franca Piras & Maria Teresa Perra

  2. Department of Surgical Sciences, Section of Pathological Anatomy, University of Cagliari, Via Ospedale, 09124, Cagliari, Italy

    Luca Pilloni

  3. Department of Medical Sciences and Public Health, University of Cagliari, Via Ospedale, 09124, Cagliari, Italy

    Luigi Minerba

  4. Omics Core and Biorepository, Sidra Medical and Research Center, Doha, Qatar

    Sara Tomei

  5. Department of Medical Sciences and Public Health, Section of Dermatology, University of Cagliari, Via Ospedale, 09124, Cagliari, Italy

    Caterina Ferreli

Authors
  1. Daniela Murtas
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Corresponding author

Correspondence to Daniela Murtas.

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Due to the retrospective nature of the study and since the analyzed clinical data of the patients were anonymous, formal consent of the patients was not required.

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The authors declare that they have no conflict of interest.

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Murtas, D., Maxia, C., Diana, A. et al. Role of epithelial–mesenchymal transition involved molecules in the progression of cutaneous melanoma. Histochem Cell Biol 148, 639–649 (2017). https://doi.org/10.1007/s00418-017-1606-0

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  • DOI: https://doi.org/10.1007/s00418-017-1606-0

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