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Phenotype characterization of human melanoma cells resistant to dabrafenib

  • Authors:
    • Fabiola Gilda Cordaro
    • Anna Lisa De Presbiteris
    • Rosa Camerlingo
    • Nicola Mozzillo
    • Giuseppe Pirozzi
    • Ernesta Cavalcanti
    • Antonella Manca
    • Giuseppe Palmieri
    • Antonio Cossu
    • Gennaro Ciliberto
    • Paolo A. Ascierto
    • Salvatore Travali
    • Eduardo J. Patriarca
    • Emilia Caputo
  • View Affiliations / Copyright

    Affiliations: Institute of Genetics and Biophysics (IGB), A. Buzzati-Traverso, CNR, I-80131 Naples, Italy, Istituto Nazionale Tumori Fondazione G. Pascale, I-80131 Naples, Italy, Unit of Cancer Genetics, Institute of Biomolecular Chemistry, CNR, I-07100 Sassari, Italy, Unit of Pathology, Hospital-University Health Unit (AOU), I-07100 Sassari, Italy, Department of Biomedical and Biotechnological Sciences-BIOMETEC, University of Catania, I-95100 Catania, Italy
    Copyright: © Cordaro et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2741-2751
    |
    Published online on: September 18, 2017
       https://doi.org/10.3892/or.2017.5963
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Abstract

In the present study, the phenotype of melanoma cells resistant to dabrafenib (a B-RAF inhibitor) was investigated, to shed more light on melanoma resistance to B-RAF inhibition. Melanoma cells resistant to dabrafenib were generated using 3 different cell lines, A375, 397 and 624.38, all carrying B-RAFV600E, and they were characterized by cytofluorometric analysis, Ion Torrent technology, immunofluorescence and biochemistry. All dabrafenib-resistant cells showed, in addition to a re-activation of MAPK signaling, morphological changes compared to their sensitive counterparts, accompanied by an increase in CD90 (mesenchymal marker) expression and a decrease in E-cadherin (epithelial marker) expression, suggesting an epithelial-to-mesenchymal-like phenotypic transition. However, melanoma cells with TGF-β1-induced epithelial-to-mesenchymal transition (EMT) were more sensitive to dabrafenib treatment compared to the sensitivity noted in the non-TGF‑β1‑induced EMT melanoma cells, suggesting that TGF-β1-induced EMT was not associated with dabrafenib resistance. Although dabrafenib-resistant cells exhibited increased cell motility and E-cadherin/vimentin reorganization, as expected in EMT, all of them showed unvaried E-cadherin mRNA and unchanged Snail protein levels, while Twist1 protein expression was decreased with the exception of A375 dabrafenib-resistant melanoma cells, where it was unaffected. These findings suggest a distinct active EMT-like process adopted by melanoma cells under drug exposure. Furthermore, dabrafenib-resistant cells exhibited stem cell-like features, with Oct4 translocation from the cytoplasm to peri-nuclear sites and nuclei, and increased CD20 expression. In conclusion, our data, in addition to confirming that resistance to dabrafenib is dependent on re-activation of MAPK signaling, suggest that this resistance is linked to a distinct active EMT-like process as well as stem-cell features adopted by melanoma cells.
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Copy and paste a formatted citation
Spandidos Publications style
Cordaro FG, De Presbiteris AL, Camerlingo R, Mozzillo N, Pirozzi G, Cavalcanti E, Manca A, Palmieri G, Cossu A, Ciliberto G, Ciliberto G, et al: Phenotype characterization of human melanoma cells resistant to dabrafenib. Oncol Rep 38: 2741-2751, 2017.
APA
Cordaro, F.G., De Presbiteris, A.L., Camerlingo, R., Mozzillo, N., Pirozzi, G., Cavalcanti, E. ... Caputo, E. (2017). Phenotype characterization of human melanoma cells resistant to dabrafenib. Oncology Reports, 38, 2741-2751. https://doi.org/10.3892/or.2017.5963
MLA
Cordaro, F. G., De Presbiteris, A. L., Camerlingo, R., Mozzillo, N., Pirozzi, G., Cavalcanti, E., Manca, A., Palmieri, G., Cossu, A., Ciliberto, G., Ascierto, P. A., Travali, S., Patriarca, E. J., Caputo, E."Phenotype characterization of human melanoma cells resistant to dabrafenib". Oncology Reports 38.5 (2017): 2741-2751.
Chicago
Cordaro, F. G., De Presbiteris, A. L., Camerlingo, R., Mozzillo, N., Pirozzi, G., Cavalcanti, E., Manca, A., Palmieri, G., Cossu, A., Ciliberto, G., Ascierto, P. A., Travali, S., Patriarca, E. J., Caputo, E."Phenotype characterization of human melanoma cells resistant to dabrafenib". Oncology Reports 38, no. 5 (2017): 2741-2751. https://doi.org/10.3892/or.2017.5963
Copy and paste a formatted citation
x
Spandidos Publications style
Cordaro FG, De Presbiteris AL, Camerlingo R, Mozzillo N, Pirozzi G, Cavalcanti E, Manca A, Palmieri G, Cossu A, Ciliberto G, Ciliberto G, et al: Phenotype characterization of human melanoma cells resistant to dabrafenib. Oncol Rep 38: 2741-2751, 2017.
APA
Cordaro, F.G., De Presbiteris, A.L., Camerlingo, R., Mozzillo, N., Pirozzi, G., Cavalcanti, E. ... Caputo, E. (2017). Phenotype characterization of human melanoma cells resistant to dabrafenib. Oncology Reports, 38, 2741-2751. https://doi.org/10.3892/or.2017.5963
MLA
Cordaro, F. G., De Presbiteris, A. L., Camerlingo, R., Mozzillo, N., Pirozzi, G., Cavalcanti, E., Manca, A., Palmieri, G., Cossu, A., Ciliberto, G., Ascierto, P. A., Travali, S., Patriarca, E. J., Caputo, E."Phenotype characterization of human melanoma cells resistant to dabrafenib". Oncology Reports 38.5 (2017): 2741-2751.
Chicago
Cordaro, F. G., De Presbiteris, A. L., Camerlingo, R., Mozzillo, N., Pirozzi, G., Cavalcanti, E., Manca, A., Palmieri, G., Cossu, A., Ciliberto, G., Ascierto, P. A., Travali, S., Patriarca, E. J., Caputo, E."Phenotype characterization of human melanoma cells resistant to dabrafenib". Oncology Reports 38, no. 5 (2017): 2741-2751. https://doi.org/10.3892/or.2017.5963
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