Intraocular Inoculation of Cutaneous Melanoma Cells in an Uveal Melanoma Animal Model

Abstract

Abstract: : Purpose: There are currently several animal models investigating cutaneous melanoma, but none of these specifically study haematogenous dissemination (HD) of the cells. Uveal melanoma (UM) and cutaneous melanoma (CM) both originate from melanocytes, however no study has yet to demonstrate differences or similarities between them. The Henry C. Witelson Ocular Pathology Laboratory, McGill University, Canada, has previously described an animal model of UM using the inoculation of human UM cells into the eyes of immunosuppressed albino rabbits with the goal of studying the HD of this disease. This is particularly important because the ocular environment is devoid of lymphatic channels. The aim of this study is to develop a new animal model of cutaneous melanoma and its haematogenous spread and to compare it to the ocular disease. Methods: Fifteen albino rabbits were injected with 1x10⁶ human CM cells (WM–266–4) into the suprachoroidal space of the eye. Animals were immunosuppressed using cyclosporin A throughout the experiment. Intraocular tumor growth was evaluated weekly by fundoscopic examination. One animal was sacrificed per week, after the 4^th week, in order to evaluate progression of the disease. The remaining animals were sacrificed at the end of the experiment. The primary tumor, lungs and liver were examined for macrometastasis. Histopathological sections of the specimens were analyzed. The results were then compared to our previous UM animal model. Results: Intraocular tumor development was found in all animals, and was detected by fundoscopy in the 2^nd week after cell implantation. The average tumor dimensions by macroscopic exam were 17mm in length, and 4.1 mm in height. Anterior chamber tumor growth was found in 66.7% of the animals. Necrosis was a prominent feature in 46.7% and was focal in 20% of the cases. Microscopic metastatic foci to the lung were observed in all rabbits. Five rabbits that were sacrificed in the 6^th, 9^th, 11^th weeks, and two rabbits from 12^th week following cell implantation presented with liver metastasis. Conclusions: We were able to produce a skin melanoma animal model that is unique in its ability to study the hematogenous dissemination of cutaneous melanoma cells. It also proved useful in highlighting the differences between cutaneous and uveal melanoma, such as more extensive anterior segment and ciliary body involvement and more numerous liver metastases in the skin melanoma model.

Keywords: melanoma • tumors