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COX-2 Silencing in Canine Malignant Melanoma Inhibits Malignant Behaviour
Tatiany L Silveira1,2, Lisa Y Pang2, Alexandra Di Domenico2
1Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
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.
Insights
Cyclooxygenase-2 (COX-2) is overexpressed in canine melanoma and drives cancer progression. Inhibiting COX-2 could be a therapeutic strategy for this aggressive cancer.
Area of Science:
- Comparative oncology
- Molecular mechanisms of cancer
Background:
- Metastatic melanoma is an aggressive cancer in humans and dogs, with dogs developing oral melanoma.
- This shared pathology presents a "One Health" opportunity for understanding melanoma progression.
- Cyclooxygenase-2 (COX-2) is implicated in melanoma's malignant behavior.
Purpose of the Study:
- To investigate the role of COX-2 in canine oral and cutaneous melanomas.
- To establish a direct relationship between COX-2 expression and melanoma's malignant behavior.
- To develop a molecular tool for studying COX-2's regulatory mechanisms in melanoma.
Main Methods:
- Analysis of 85 canine melanomas for COX-2 overexpression.
- Development of canine melanoma cell lines with inducible COX-2 inhibition using micro-RNA (miRNA).
- Assessment of cellular proliferation, migration, and invasion in response to COX-2 modulation.
Main Results:
- COX-2 is overexpressed in canine oral and cutaneous melanomas.
- COX-2 expression correlates with poor prognostic markers.
- Cellular proliferation, migration, and invasion are dependent on COX-2 activity.
- A novel molecular tool for COX-2 research in melanoma was created.
Conclusions:
- COX-2 plays a critical role in the malignant behavior of canine melanoma.
- Targeting COX-2 may offer a therapeutic approach for canine melanoma.
- The developed tool facilitates further research into COX-2's mechanisms in melanoma progression.
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