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Marta Kilian, Karin Loeffler, Hans Grossniklaus, Frank Holz, Christiane Pfarrer, Christian Kurts, Martina Herwig; Comparison of Two Melanoma Cell Lines as Mouse-Models of Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4203.
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The purpose of this study was to compare the immunologic, growth and metastatic characteristics of HCmel12, a new murine macrophage-attractive skin melanoma cell line, and B16LS9 melanoma cells in a murine ocular melanoma model.
Eight CX3CR1 GFP knock-in mice and eight C57Bl/6 mice were injected intravitreally with HCmel12 or B16LS9 melanoma cells. The latter represent a previously established mouse-model for uveal melanoma when injected intravitreally. Local tumor growth and distribution of macrophages in CX3CR1 GFP knock-in mice were verified in vivo by scanning laser ophthalmoscopy. Tumor characteristics such as inflammation, tumor invasion into the uvea, extrascleral growth and sites of metastases were monitored histologically. Draining lymph nodes were investigated by immunohistochemistry with HMB45/MART-1 markers for melanoma cells. Immunohistochemical stains were performed for F4/80 and CD163 to identify macrophages and their subtypes.
HCmel12 and B16LS9 cells grew intravitreally resulting in solid tumor growth in all mice within two days after injection. Both melanoma cell lines invaded the uvea and proceeded to extraocular extension if enucleation was not performed after 5-9 days. Distant metastases were found in the lung for HCmel12 cells and in the liver and spleen for B16LS9 cells. For HCmel12 cells, they occurred only after extrascleral tumor growth and under participation of the lymphatic system. Both tumors exhibited inflammatory cells including macrophages.
Both melanoma cell lines showed similar characteristics in terms of local and extraocular tumor growth and they both exhibited involvement of draining lymph nodes. Metastatic behaviour was not influenced by the ocular microenvironment since both cell lines showed the same metastatic behaviour when injected subcutaneously. However, due to the fact that distant metastases of HCmel12 cells established exclusively in the lung they do not qualify as a model of uveal melanoma.
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