GANGLIOSIDES IN HUMAN UVEAL MELANOMA METASTATIC PROCESS

The inability of current therapy to prevent metastases arising from uv eal melanoma often results in patient mortality. With the goal of deve loping a treatment for metastasis, gangliosides were studied as potent ial tumor-associated antigens. Our report describes the production of a metastatic liver variant (MH) from a human uveal melanoma cell line (SP6.5). Cells were injected into nude mouse spleens and liver metasta ses collected 2 months later. After 21 days of in vitro subculture, th e cells were re-injected into normal nude mice spleen; 10 cycles (MH10 ) were performed. Gangliosides were extracted, purified, chromatograph ed on HPTLC plates and sprayed with a resorcinol-HCl reagent, the sial ic acid spots being quantified by densitometry. Gangliosides were anal yzed in each metastatic liver variant and compared with the SP6.5 s.c. tumor. The results showed a significant increase in GM3 and a signifi cant decrease in GD3 and GD2 in the last metastatic variants obtained (MH5, MH8, MH9 and MH10) compared with the primary s.c. tumor, SP6.5. Such evolution in the ganglioside pattern was maintained throughout th e progression of the different liver variants. Our results indicate th at precursor ganglioside GM3 and gangliosides GD3 and GD2 could be ass ociated with neoplastic evolution of malignancy of human uveal melanom a in nude mice. (C) 1996 Wiley-Liss, Inc.