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Article Open Access

NF‑κB inhibition is associated with OPN/MMP‑9 downregulation in cutaneous melanoma

  • Authors:
    • Claudio Guarneri
    • Valentina Bevelacqua
    • Jerry Polesel
    • Luca Falzone
    • Patrizia S. Cannavò
    • Demetrios A. Spandidos
    • Grazia Malaponte
    • Massimo Libra
  • View Affiliations / Copyright

    Affiliations: Department of Clinical and Experimental Medicine, Section of Dermatology, University of Messina, I‑98125 Messina, Italy, Department of Biomedical and Biotechnological Sciences, Section of General and Clinical Pathology and Oncology, University of Catania, I‑95124 Catania, Italy, Unit of Cancer Epidemiology, CRO Aviano National Cancer Institute, IRCCS, I‑33081 Aviano, Italy, Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion 71003, Greece
    Copyright: © Guarneri et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 737-746
    |
    Published online on: January 10, 2017
       https://doi.org/10.3892/or.2017.5362
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Abstract

The development of cutaneous melanoma is influenced by genetic factors, including BRAF mutations and environmental factors, such as ultraviolet exposure. Its progression has been also associated with the involvement of several tumour microenvironmental molecules. Among these, nuclear factor‑κB (NF‑κB) has been indicated as a key player of osteopontin (OPN) and matrix metalloproteinase‑9 (MMP‑9) activation. However, whether NF‑κB plays a role in the development and progression of melanoma in association with the OPN/MMP‑9 axis according to the BRAFV600E mutation status has not been investigated in detail to date. Thus, in the present study, in order to shed light on this matter, 148 patients with melanoma and 53 healthy donors were recruited for the analysis of OPN, MMP‑9 and NF‑κB. Significantly higher circulating levels of OPN and MMP‑9 were observed in the patients with melanoma when compared to the healthy donors. Similar data were obtained for NF‑κB p65 activity. The OPN levels did not differ significantly between melanomas with or without BRAFV600E mutation. However, as regards NF‑κB and MMP‑9, significant differences were observed between the melanomas with or without BRAFV600E mutation. To determine whether NF‑κB inhibition is associated with a decrease in the levels of OPN and MMP‑9, peripheral blood mononuclear cells from 29 patients with melanoma were treated with the NF‑κB inhibitor, dehydroxymethylepoxyquinomycin (DHMEQ), with or without OPN. As expected, the inhibition of NF‑κB induced a marked decrease in both the OPN and MMP‑9 levels. Furthermore, the decrease in MMP‑9 levels was higher among melanomas harbouring the BRAFV600E mutation. Overall, our data suggest that the activation of MMP‑9 is associated with the BRAFV600E mutation status. Furthermore, such an activation is mediated by NF‑κB, suggesting its role as therapeutic target in patients with melanoma.
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Copy and paste a formatted citation
Spandidos Publications style
Guarneri C, Bevelacqua V, Polesel J, Falzone L, Cannavò PS, Spandidos DA, Malaponte G and Libra M: NF‑κB inhibition is associated with OPN/MMP‑9 downregulation in cutaneous melanoma. Oncol Rep 37: 737-746, 2017.
APA
Guarneri, C., Bevelacqua, V., Polesel, J., Falzone, L., Cannavò, P.S., Spandidos, D.A. ... Libra, M. (2017). NF‑κB inhibition is associated with OPN/MMP‑9 downregulation in cutaneous melanoma. Oncology Reports, 37, 737-746. https://doi.org/10.3892/or.2017.5362
MLA
Guarneri, C., Bevelacqua, V., Polesel, J., Falzone, L., Cannavò, P. S., Spandidos, D. A., Malaponte, G., Libra, M."NF‑κB inhibition is associated with OPN/MMP‑9 downregulation in cutaneous melanoma". Oncology Reports 37.2 (2017): 737-746.
Chicago
Guarneri, C., Bevelacqua, V., Polesel, J., Falzone, L., Cannavò, P. S., Spandidos, D. A., Malaponte, G., Libra, M."NF‑κB inhibition is associated with OPN/MMP‑9 downregulation in cutaneous melanoma". Oncology Reports 37, no. 2 (2017): 737-746. https://doi.org/10.3892/or.2017.5362
Copy and paste a formatted citation
x
Spandidos Publications style
Guarneri C, Bevelacqua V, Polesel J, Falzone L, Cannavò PS, Spandidos DA, Malaponte G and Libra M: NF‑κB inhibition is associated with OPN/MMP‑9 downregulation in cutaneous melanoma. Oncol Rep 37: 737-746, 2017.
APA
Guarneri, C., Bevelacqua, V., Polesel, J., Falzone, L., Cannavò, P.S., Spandidos, D.A. ... Libra, M. (2017). NF‑κB inhibition is associated with OPN/MMP‑9 downregulation in cutaneous melanoma. Oncology Reports, 37, 737-746. https://doi.org/10.3892/or.2017.5362
MLA
Guarneri, C., Bevelacqua, V., Polesel, J., Falzone, L., Cannavò, P. S., Spandidos, D. A., Malaponte, G., Libra, M."NF‑κB inhibition is associated with OPN/MMP‑9 downregulation in cutaneous melanoma". Oncology Reports 37.2 (2017): 737-746.
Chicago
Guarneri, C., Bevelacqua, V., Polesel, J., Falzone, L., Cannavò, P. S., Spandidos, D. A., Malaponte, G., Libra, M."NF‑κB inhibition is associated with OPN/MMP‑9 downregulation in cutaneous melanoma". Oncology Reports 37, no. 2 (2017): 737-746. https://doi.org/10.3892/or.2017.5362
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