COX-2 Silencing in Canine Malignant Melanoma Inhibits Malignant Behaviour

Frontiers in Veterinary Science

Emerson S. Veloso¹  Helen L. Del Puerto¹  Istéfani L. D. Silva¹  Enio Ferreria¹  Lisa Y. Pang²  Alexandra Di Domenico²  David J. Argyle²  Tatiany L. Silveira² 

[1] 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;

关键词: melanoma;    COX-2;    canine;    malignant;    one health;   

DOI  :  10.3389/fvets.2021.633170

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown