Intravitreally Injected HCmel12 Melanoma Cells Serve as a Mouse Model of Tumor Biology of Intraocular Melanoma

Abstract

Purpose: To establish a mouse model with histologic characteristics of uveal melanoma for investigation of intraocular tumor biology of melanoma.Methods: After injection of 1 × 105 of HCmel12 melanoma cells, a cutaneous melanoma cell line, into the vitreous of CX3CR1+/GFP or C57Bl/6 mice (n = 12), tumor growth patterns, clinicopathological features, angiogenesis and metastatic behavior were analyzed by histology (hematoxylin and eosin, periodic acid-Schiff without hematoxylin) and immunohistochemistry (HMB45/MART-1-Ab, F4/80-Ab, green fluorescent protein (GFP)-Ab and VE-cadherin-Ab).Results: HCmel12 cells formed intraocularly growing tumor masses, which showed histologic features of intraocular melanoma such as angiotropism, intratumoral endothelial-lined vasculature, vasculogenic mimicry including prognostic significant extravascular matrix patterns, and invasion by inflammatory cells, in particular macrophages. There was no difference in tumor growth characteristics between CX3CR1+/GFP and C57Bl/6 mice. Five of 10 mice proceeded to extrascleral tumor growth and three of these developed metastases.Conclusions: Intraocularly injected HCmel12 cells developed tumor masses with histologic characteristics of aggressive melanoma similar to human uveal melanoma. Since hematogenous dissemination to the liver was not observed, intravitreally injected HCmel12 cells do not qualify as a model for metastasizing intraocular melanoma. However, since the eye represents a semi-closed compartment with access to constant blood supply, these intraocular tumors represent a model for studies of isolated parameters in general tumor biology of intraocular melanoma.