Effect of anti-ganglioside antibodies on the metastatic spread of intraocular melanomas in a nude mouse model of human uveal melanoma.
In vivo and in vitro studies were performed to determine: (a) if human uveal melanoma cells expressed GD2 and GD3 gangliosides; (b) if anti-GD2 monoclonal antibodies would inhibit the propensity of human uveal melanoma cells to localize in the liver following intravenous injection; and (c) if anti-GD2 monoclonal antibody would reduce the spontaneous metastasis of primary intraocular melanomas in nude mice. The results showed that all three of the human uveal melanoma cell lines tested expressed GD2 and GD3 gangliosides in vitro and in vivo. The human uveal melanoma cell lines preferentially localized in the liver and entered the hepatic parenchyma following spontaneous metastasis from the eyes of nude mice. In vivo administration of anti-GD2 monoclonal antibody produced a sharp reduction in the number of uveal melanoma cells that disseminated to the liver following either intravenous injection or by spontaneous metastasis from primary intraocular melanomas. Collectively, the results demonstrate that uveal melanoma cells display a propensity to localize in the liver after entering the bloodstream; however, this localization can be significantly inhibited by in vivo administration of anti-ganglioside antibodies. The expression of GD2 and GD3 surface gangliosides on uveal melanomas and the capacity of anti-ganglioside antibodies to inhibit metastasis formation in mouse models of ocular and cutaneous melanomas raise the possibility of implementing anti-ganglioside antibodies as potential therapeutic agents for the management of uveal melanoma.
Niederkorn
J Y
JY
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas 75235.
Mellon
J
J
Pidherney
M
M
Mayhew
E
E
Anand
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D005732:Gangliosides / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
D000911:Antibodies, Monoclonal; D005732:Gangliosides; C026226:ganglioside, GD3; C019403:ganglioside, GD2