COX-2 Silencing in Canine Malignant Melanoma Inhibits Malignant Behaviour

Tatiany Silveira, Lisa Pang, Alexandra Di Domenico, Emerson S. Veloso, Istéfani L. D. Silva, Helen L. Del Puerto, Enio Ferreria, David Argyle

Research output: Contribution to journalArticlepeer-review

Abstract

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
Original languageEnglish
Article number633170
JournalFrontiers in Veterinary Science
Volume8
Early online date26 Aug 2021
DOIs
Publication statusE-pub ahead of print - 26 Aug 2021

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