COX-2 Silencing in Canine Malignant Melanoma Inhibits Malignant Behaviour.

Autor:	Silveira TL; Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, Brazil.; Royal (Dick) School of Veterinary Studies, Roslin Institute, The University of Edinburgh, Edinburgh, United Kingdom., Pang LY; Royal (Dick) School of Veterinary Studies, Roslin Institute, The University of Edinburgh, Edinburgh, United Kingdom., Di Domenico A; Royal (Dick) School of Veterinary Studies, Roslin Institute, The University of Edinburgh, Edinburgh, United Kingdom., Veloso ES; Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, Brazil., Silva ILD; Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, Brazil., Puerto HLD; Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, Brazil., Ferreria E; Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, Brazil., Argyle DJ; Royal (Dick) School of Veterinary Studies, Roslin Institute, The University of Edinburgh, Edinburgh, United Kingdom.
Jazyk:	angličtina
Zdroj:	Frontiers in veterinary science [Front Vet Sci] 2021 Aug 26; Vol. 8, pp. 633170. Date of Electronic Publication: 2021 Aug 26 (Print Publication: 2021).
DOI:	10.3389/fvets.2021.633170
Abstrakt:	Metastatic melanoma is a very aggressive form of cancer in both humans and dogs. Dogs primarily develop oral melanoma of mucosal origin. Although oral melanoma in humans is rare, both diseases are highly aggressive with frequent metastases. This disease represents a "One Health" opportunity to improve molecular and mechanistic understanding of melanoma progression. Accumulating evidence suggests that cyclooxygenase-2 (COX-2) may play a critical role in the malignant behaviour of melanoma. In this study we analysed 85 histologically confirmed melanomas from canine patients and showed that COX-2 is overexpressed in both oral and cutaneous melanomas and that COX-2 expression correlates with established markers of poor prognosis. To determine the role of COX-2 in melanoma we developed two melanoma cell lines with stable integration of an inducible doxycycline-regulated expression vector containing a COX-2 targeted micro-RNA (miRNA). Using this system, we showed that cellular proliferation, migration and invasion are COX-2 dependent, establishing a direct relationship between COX-2 expression and malignant behaviour in canine melanoma. We have also developed a powerful molecular tool to aid further dissection of the mechanisms by which COX-2 regulates melanoma progression. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Silveira, Pang, Di Domenico, Veloso, Silva, Puerto, Ferreria and Argyle.)
Databáze:	MEDLINE
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