Abstract
BackgroundMetastatic melanoma is one of the most aggressive forms of cancer in humans. Among its types, mucosal melanomas represent one of the most highly metastatic and aggressive forms, with a very poor prognosis. Because they are rare in Caucasian individuals, unlike cutaneous melanomas, there has been fewer epidemiological, clinical and genetic evaluation of mucosal melanomas. Moreover, the lack of predictive models fully reproducing the pathogenesis and molecular alterations of mucosal melanoma makes its treatment challenging. Interestingly, dogs are frequently affected by melanomas of the oral cavity that are characterized, as their human counterparts, by focal infiltration, recurrence, and metastasis to regional lymph nodes, lungs and other organs. In dogs, some particular breeds are at high risk, suggesting a specific genetic background and strong genetic drivers. Altogether, the striking homologies in clinical presentation, histopathological features, and overall biology between human and canine mucosal melanomas make dogs invaluable natural models with which to investigate tumor development, including tumor ætiology, and develop tailored treatments.MethodsWe developed and characterized two canine oral melanoma cell lines from tumors isolated from dog patients with distinct clinical profiles; with and without lung metastases. The cells were characterized using immunohistochemistry, pharmacology and genetic studies.ResultsWe have developed and immunohistochemically, genetically, and pharmacologically characterized. Two cell lines (Ocr_OCMM1X & Ocr_OCMM2X) were produced through mouse xenografts originating from two clinically contrasting melanomas of the oral cavity. Their exhaustive characterization showed two distinct biological and genetic profiles that are potentially linked to the stage of malignancy at the time of diagnosis and sample collection of each melanoma case. These cell lines thus constitute relevant tools with which to perform genetic and drug screening analyses for a better understanding of mucosal melanomas in dogs and humans.ConclusionsThe aim of this study was to establish and characterize xenograft-derived canine melanoma cell lines with different morphologies, genetic features and pharmacological sensitivities that constitute good predictive models for comparative oncology. These cell lines are relevant tools to advance the use of canine mucosal melanomas as natural models for the benefit of both veterinary and human medicine.
Highlights
In humans, melanoma is one of the most aggressive types of cancer
Tumor samples Melanoma tumor tissues were obtained from a 14-year-old Yorkshire Terrier (TS1, Tumor sample 1) and an 11-year-old German Shepherd (TS2, Tumor sample 2) that presented at the clinic with melanocytic lesions of the oral cavity with and without metastasis to the lungs (Table 1)
Both tumors were in the oral cavity but presented different WHO stage at the time of diagnosis and samples collection (Table 1)
Summary
Whereas cutaneous forms represent the most common cases, melanoma of the oral cavity is rare but very aggressive, highly metastatic [1] and associated with frequent relapse and poor outcomes [2]. These forms mainly arise in the sino-nasal cavity (more than 73% of cases) and are highly immunogenic tumors contributing to an immune anti-tumor reaction that can lead to tumor escape and resistance to most standard treatment protocols [3]. Mucosal melanomas represent one of the most highly metastatic and aggressive forms, with a very poor prognosis. The striking homologies in clinical presentation, histopathological features, and overall biology between human and canine mucosal melanomas make dogs invaluable natural models with which to investigate tumor development, including tumor ætiology, and develop tailored treatments
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