97th DOG Annual Meeting 1999
ANIMAL MODEL FOR HUMAN METASTATIC UVEAL MELANOMA
S. Dithmar1,3, A. I. Wallace2, H. E. Grossniklaus1
In order to develop a murine ocular melanoma model, intraocularly injected murine and human uveal melanoma cell lines were examined for their capability to produce hepatic metastasis.
Methods: Groups of immune competent C57BL6 (C57) and T cell depleted athymic nude Balb-c (ANB) mice (n=10/group) were inoculated into the posterior compartment (PC) with 5X105/5ml B16F10 Queens melanoma cells. Groups of NK/T cell depleted beige nude x-linked immune deficient (BNX) mice were inoculated into the PC with 5X104-5X105/5ml human uveal melanoma cell lines (MEL270, MEL285, MEL290, OMM2.3). Expression of MHC class I antigens was determined by FACS analysis for each cell line. The eyes were enucleated at 2 weeks and the animals were sacrificed at 4 weeks post-inoculation. Examination of histologic sections was used to determine tumor growth in the eye and the number of metastases in the lungs and liver.
Results: All C57 and ANB mice exhibited tumor growth and metastases. The average numbers of liver micrometastases were 28 (C57) and 9 (ANB). The Queens cells failed to express MHC class I antigens. Tumor growth and liver micrometastases (average 3.4) were seen in all mice receiving 5X105/5ml MEL270. The human melanoma cell lines expressed MHC class I antigens.
Conclusions: The presented animal model is suitable for the simulation of metastatic uveal melanoma. B16-F10 Queens cells are susceptible to NK-cell mediated lysis because of their lack of MHC class I expression. Inoculated T cell depleted mice (ANB) do not show increased metastatic rates.
Supported by Kusen Foundation, Germany (Di 98/99), RPB Inc, Fight for Sight, and NIH EY06360
Departments of 1Ophthalmology and 2Dermatology,
Emory University School of Medicine, Atlanta, Georgia;